# ent

id: cord-007373-livz5zuu
type: PROTEIN
entity:
  heparinbinding protein 1a7s Bacillus intermedius glutamyl endopeptidase 1p3c bovine beta trypsin 5ptp


id: cord-252166-qah877pk
type: GGP
entity:
  serotonin 5 HT 2A 5 HT 2B and 5 HT 2C receptor antagonists synthesis pharmacology 3D QSAR and molecular modeling of aminoalkyl benzo


id: cord-287450-hydy874v
type: GGP
entity:
  PPARα γ dual agonists whose profile seems well suited for addressing both hyperglycemia as well as the enhanced cardiovascular risk of diabetic patients 34 Annalisa Pastore


id: cord-018133-2otxft31
type: DISEASE
entity:
  Weaver 1976 Levitt 1983 The most important development to support the emergence of bioinformatics however


id: cord-000822-iuglkdcp
type: GGP
entity:
  ¼ Â sim½s i ðxÞ s j ðyÞ À Â fw½s i ðxÞ þ w½s j ðyÞg À Â dissim½s i ðxÞ s j ðyÞ Only structure element


id: cord-018401-josb16pi
type: PROTEIN
entity:
  Ac V 6 R 2 NH 2 Ac V 6 K 2 NH 2 Ac A 6 K NH 2 Ac I 6 K 2 NH 2 Ac A 6 K OH DA 6 NH 2 Ac V 6 D 2 NH 2 Ac A 6 D OH KA 6 NH 2


id: cord-018401-josb16pi
type: GGP
entity:
  Surface plasmon resonance spectroscopy Atomic force microscopy Investigation of the kinetics of self assembly conduct structure manipulation determine the size and morphology of the nanostructures


id: cord-018401-josb16pi
type: CHEMICAL
entity:
  aromatic p stacking between the aromatic rings of the pyrenyl structure dominates At neutral pH though the amino


id: cord-346546-yffwd0dc
type: CHEMICAL
entity:
  afford 2S 3S 2 acetamido N 3 bromoprop 2 yn S 2 Acetamido N 1 3 bromoprop 2 yn 1 yl succinimide asparagine


id: cord-322885-ob5euspo
type: CHEMICAL
entity:
  N terminal loop region of domain III to form the active site that is an important drug target area Fig 2C fig S7 The N terminal loop of domain III


id: cord-009660-23cdi61w
type: GGP
entity:
  Burkitt s lymphoma Brit Alerl J 2 Chandra S tlndulating tubules associated with endoplasmic reticullnu


id: cord-010260-8lnpujip
type: DNA
entity:
  group I introns Grivell 1994 Posttranslational modifications like phosphorylation glycosylation sulfation methylation farnesylation prenylation


id: cord-103823-3rchp9yy
type: DNA
entity:
  e Boolarra virus Pariacoto virus Striped jack nervous necrosis virus Greasy grouper nervous necrosis virus


id: cord-264489-h1n9ywbd
type: DNA
entity:
  X ray structures 3WO2 3WO3 3WO4 and 3F62 are 2 33 Å 3 10 Å 3 10 Å and 2 00 Å respectively Nanoscale Molecular Dynamics NAMD and Visual Molecular Dynamics VMD programs


id: cord-264489-h1n9ywbd
type: DISEASE
entity:
  simian immunodeficiency virus SIV SIVhuman immunodeficiency virus SHIV and HIV type 1 HIV 1 transmission Interleukin


id: cord-254107-02bik024
type: PROTEIN
entity:
  epidermal growth factor receptor tyrosine kinase protein 35 36 Bruton s tyrosine kinase 37 Janus kinase 3 38


id: cord-292985-w62xaa4f
type: PROTEIN
entity:
  SARS CoV 2 Spike Glycoprotein Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion Structure


id: cord-292985-w62xaa4f
type: LAW
entity:
  Structures of Two Coronavirus Main Proteases Implications for Substrate Binding and Antiviral Drug Design Targeting the Dimerization of the Main Protease of Coronaviruses A Potential Broad Spectrum Therapeutic Strategy Structure of M


id: cord-292985-w62xaa4f
type: LAW
entity:
  Structure and Function in Homodimeric Enzymes Simulations of Cooperative and Independent Functional Motions


id: cord-312946-p2iazl7z
type: PROTEIN
entity:
  red artocarpin 1vbo blue heltuba 1c3m magenta parkia lectin 1zgs yellow calsepa 1ouw pink banana lectin 2bmz black jacalin 1ugw violet AHL 1toq


id: cord-312946-p2iazl7z
type: DISEASE
entity:
  human immunodeficiency virusinhibitory glycoprotein from the marine sponge Niphates erecta Processing of X


id: cord-102463-d440jsek
type: WORK_OF_ART
entity:
  ProGen Language Modeling for Protein Generation preprint Synthetic Biology Generating Tertiary Protein Structures


id: cord-102463-d440jsek
type: ORG
entity:
  Generative Adversarial Networks Generalized Latent Variable Recovery for Generative Adversarial Networks Shape


id: cord-102463-d440jsek
type: ORG
entity:
  the U S Department of Energy Office of Science Office of Advanced Scientific Computing Research Scientific


id: cord-015619-msicix98
type: WORK_OF_ART
entity:
  Pos Methods for Multiscale Stochastic Simulation of Molecular Self Assembly Tiequan Zhang Carnegie Mellon University Pittsburgh PA USA Macromolecular


id: cord-013387-q91052qw
type: DNA
entity:
  hCOX 2 receptor LMQC72 G 11 0 kcal mol LMQC36 G 10 6 kcal mol and LMQC50 G 10 2 kcal mol LMQC72 and LMQC36


id: cord-013387-q91052qw
type: ORG
entity:
  the Computer aided Drug Design An Overview Octanol Water Partition Coefficients of Simple Organic Compounds Predicting a Drug s Membrane Permeability A Computational Model Validated


id: cord-292483-u0ycqelc
type: PROTEIN
entity:
  cord 292483 u0ycqelc authors Rossmann Michael G Battisti Anthony J Plevka Pavel title Future prospects date 2011 04 16 journal Adv Protein


id: cord-292483-u0ycqelc
type: ORG
entity:
  International Tables for Crystallography Volume F Crystallography of Biological Macromolecules Structure


id: cord-017181-ywz6w2po
type: RNA
entity:
  Tryptophan Operon RNA hairpin loop stability depends on closing base pair Coaxial Stacking of Helixes Enhances Binding of Oligoribonucleotides and Improves Predictions of RNA


id: cord-017181-ywz6w2po
type: WORK_OF_ART
entity:
  Combining Micro and Macro Modeling in DEVS for Computational Biology Theory of Modeling and Simulation One


id: cord-014685-ihh30q6f
type: PROTEIN
entity:
  hydrophobic helical peptide P Chetal V Chauhan D Sahal International Centre For Genetic Engineering Biotechnology


id: cord-014685-ihh30q6f
type: PROTEIN
entity:
  post termination complex P Guo L Zhang Y Feng G Jing Institute of Biophysics Chinese Academy of Sciences National Laboratory of Biomacromolecules Beijing China Ribosome recycling factor RRF


id: cord-014685-ihh30q6f
type: PROTEIN
entity:
  L chain apoferritin K Yoshizawa 1 K Iwahori 3 Y Mishima 1 I Yamashita 2 1 CREST JST 2 ATRL Matsushita 3 Nara Institute of Science and Technology The denaturation of apoferritin


id: cord-014685-ihh30q6f
type: PROTEIN
entity:
  carbonic anhydrase H M Becker J W Deitmer Abt Allgem Zoologie TU Kaiserslautern 67663 Kaiserslautern


id: cord-014685-ihh30q6f
type: PROTEIN
entity:
  prostaglandin endoperoxide H2 synthase Prostaglandin endoperoxide H 2 synthases 1 and 2 PGHS 1 and 2


id: cord-014685-ihh30q6f
type: PROTEIN
entity:
  nucleoprotein complex K Zupán 1 L Herényi 1 K Tóth 2 Z Majer 3 G Csík 1 1 Institute of Biophysics and Radiation Biology Semmelweis Univ Budapest Hungary 2 Biophysics of Macromolecules German Cancer Research Center Heidelberg Germany 3 Department of Organic Chemistry Eötvös Loránd


id: cord-014685-ihh30q6f
type: DNA
entity:
  HIV 1 genomic RNA S Bernacchi 2 E Ennifar 1 K Toth 2 P Walter 1 J Langowski 2 P Dumas 1 1 CNRS UPR 9002 Strasbourg France 2 DKFZ Heidelberg Germany


id: cord-014685-ihh30q6f
type: DNA
entity:
  CUG repeats Y Sato K Kimura A Takénaka Graduate School of Bioscience and Biotechnology Tokyo Institute of Technology Yokohama Japan


id: cord-014685-ihh30q6f
type: GGP
entity:
  Refs 1 2 3 XAS spectroscopy results show that there are two different structures of the metal binding site


id: cord-014685-ihh30q6f
type: CHEBI
entity:
  cholesterol proteoliposomes M Berchel 1 J Jeftic 1 T Benvegnu 1 J Y Thepot 2 D Plusquellec 1 1 ENSCR


id: cord-014685-ihh30q6f
type: GGP
entity:
  speci c conductance s of aqueous solution of electrolytes viz NaF NaCl NaNO 3 Na2SO 4 KF KCl KNO 3 K 2 SO 4 MgCl 2 CaCl 2 FeCl 3 MnCl 2 CrCl 3 CuCl 2 CoCl 2


id: cord-014685-ihh30q6f
type: CL
entity:
  stem bulge stem region of DIS39 and the solution structures of DIS39 in the kissing loop and extendedduplex


id: cord-014685-ihh30q6f
type: PRODUCT
entity:
  J C Holyoake M S Sansom Biochemistry Department University of Oxford South Parks Road Oxford OX1 3QU


id: cord-014685-ihh30q6f
type: ORG
entity:
  Department of Animal Physiology and Biophysics Faculty of Biology University of Bucharest 2 Department of Biochemistry Faculty of Biology University of Bucharest Bucharest Romania Hypericin Hyp


id: cord-014685-ihh30q6f
type: WORK_OF_ART
entity:
  Faculty of Science and Technology Keio University Japan 2 Japan Synchrotron Radiation Research Institute


id: cord-014685-ihh30q6f
type: ORG
entity:
  NMR 2 Department of Surgery 3 Department of Radiotherapy All India Institute of Medical Sciences New Delhi India Diffusion


id: cord-014685-ihh30q6f
type: ORG
entity:
  Applied Physics College of Humanities and Sciences Nihon University 2 Department of Biophysics and Life


id: cord-014685-ihh30q6f
type: ORG
entity:
  University of Helsinki Finland 2 Institute of Biotechnology University of Helsinki Finland Molecular


id: cord-014685-ihh30q6f
type: CHEMICAL
entity:
  Ruysshaert 2 B Bechinger 1 1 ULP CNRS Chemistry 4 rue Blaise Pascal 67070 Strasbourg 2 Université Libre Campus Plaine


id: cord-023726-2fduzqyb
type: PROTEIN
entity:
  T 7 L VP1 VP2 VP3 VP1 VP2 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP3 FIGURE 2 7 Arrangement


id: cord-023726-2fduzqyb
type: GGP
entity:
  T 7 L VP1 VP2 VP3 VP1 VP2 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP1 VP2 VP3 VP3 FIGURE 2 7


id: cord-314329-rzda8x62
type: CHEMICAL
entity:
  N 5 methylisoxazol 3 yl carbonyl alanyl L valyl N 1 1R 2Z 4 benzyloxy 4 oxo 1 3R 2oxopyrrolidin 3 yl methyl but 2 enyl L leucinamide chain C of the structure hereinafter N3 This inhibitor


id: cord-031957-df4luh5v
type: CHEMICAL
entity:
  defensin like antifungal peptide from Trigonella foenum graecum fenugreek seeds Antimicrobial peptides pore formers


id: cord-031957-df4luh5v
type: CHEMICAL
entity:
  stinging nettle Urtica dioica rhizomes Hevein like antimicrobial peptides of plants Structural basis for chitin


id: cord-314321-klb8oe9q
type: WORK_OF_ART
entity:
  Structure Function and Antigenicity of the SARS CoV 2 Spike Glycoprotein Structure of the SARS CoV 2


id: cord-301827-a7hnuxy5
type: CHEBI
entity:
  molecular complexes 1 4 11 12 13 14 15 31 70 71 72 73 76 77 78 79 131 132 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 The conformational plasticity of IDPs


id: cord-330590-nu8ckeud
type: CELL_TYPE
entity:
  mammalian super tree hosts Bininda Emonds et al 2007 with the picante package We include the body mass litter size number of litters per year and trophic guild


id: cord-355327-d3gcfepx
type: PROTEIN
entity:
  Clostridium acetobutylicum thymidine kinase 1 1xx6 E coli aspartate transcarbamylase 2 1r0b 3 1tug Thermotoga maritima


id: cord-355327-d3gcfepx
type: PROTEIN
entity:
  GAPDH glyceraldehyde 3 phosphate dehydrogenase GEF guanine nucleotide exchange factor GGA1 golgi localized c adaptin Grp1 guanine nucleotide exchange factor


id: cord-355327-d3gcfepx
type: PROTEIN
entity:
  integrin binding protein homolog grp1 Grx glutathione reductase PCBP2 poly C binding protein 2 pHsam domain


id: cord-355327-d3gcfepx
type: SO
entity:
  domain PNMT phenylethanolamine N methyltransferase RuBisCoL ribulose 1 5 bisphosphate carboxylase oxygenase


id: cord-355327-d3gcfepx
type: GGP
entity:
  SAM S adenosyl L methionine VEGF vascular endothelial growth factor Ae Aeropyrum pernix Af Archaeoglobus fulgidus BPV bovine papilloma virus Cr Crithidia fasciculata Dm Drosophila


id: cord-330427-3eoio8uk
type: PROTEIN
entity:
  amino acid statine Renin inhibitors Synthesis of transition state analogue inhibitors containing phosphorus acid derivatives


id: cord-313694-p2sgaypq
type: PROTEIN
entity:
  asparagine linked tri and tetraantennary glycopeptides containing GlcNAc 13 1 6 Man a 1 6 Man and poly Nacetyllactosamine sequences


id: cord-023284-i0ecxgus
type: PROTEIN
entity:
  ligand Abtstr 236 239 Quant Struct Act Relat 9 234 293 1990 binding unfolding kinetics conformational equilibria


id: cord-023284-i0ecxgus
type: PROTEIN
entity:
  type I 3 phenoxybenzyl 2 4 ethoxyphenyl 3 3 3 trifluoropropyl ether R Quant Struct Act Relat 9 234 293 1990 Abstr 308 271 isomer 11 a cyano 3 phenoxybenzyl 2 4 chlorophenyl 2 methylpropionate S isomer III


id: cord-023284-i0ecxgus
type: PROTEIN
entity:
  I 11 OH 0 Ho2C Quant Struct Act Relat 9 234 293 1990 Abstr 321 322 279 Biological material a Aspergillus ochraceus b Carbopeptidase A


id: cord-023284-i0ecxgus
type: DNA
entity:
  X ray structure d The combination of NMR and molecular modeling approaches however makes it possible to model virtually any molecule


id: cord-023284-i0ecxgus
type: GGP
entity:
  acetylcholine histamine cortisonelhydrocortisone indole 3 acetic acid phenoxyacetic acid herbicides c


id: cord-023284-i0ecxgus
type: GGP
entity:
  isosorbide l 1 5 monoacetate 1 2 monoacetate 1 5 mononitrate 1 2 mononitrate l diacetate 1 5 nitro 2 acetate 1 2 nitro 5 acetate l dinitrate Rn R I retention factors


id: cord-023284-i0ecxgus
type: CHEMICAL
entity:
  methyl 2 nitropheno1 2 4dichlorophenol 2 4 6 trichlorophenol 2 3 4 5 tetrachlorophenol 2 4 6 triiodophenol pentachlorophenol


id: cord-023284-i0ecxgus
type: CHEMICAL
entity:
  3 6a dihydroxy 8 9 methylenedioxy pterocarpan 6a 1 la dehydropisatin 3 hydroxy 8 9 methylenedioxy 6a 1 1 a dehydropterocarpan 3 hydroxy 9 methoxypterocarpan 3 hydroxy 9 zmethoxypterocarpan 3 zhydroxy 9 methoxypterocarpan vestitol sativan


id: cord-023284-i0ecxgus
type: CHEMICAL
entity:
  2 C1 3 C1 2 4 5 Cl 2 4 6 CI pentachlorophenol 4 CI 2 Me 4 C1 3 Me 4 C1 2 3 Me 4 C1 3 5 Me 4 CI 2 ally1 4 C1 2 Pr 5 Me 4Z1 2 3 C1 2 443 2 5 C1 2 6 Cl 3 4 C1 3 5 CI 2 3 6 C1 2 Cl 6 NO2 2 4 C1


id: cord-023284-i0ecxgus
type: CHEMICAL
entity:
  N substituted 3 methyl 4 nitropyrazole 5 carboxamides 11 6 N substituted 4 amino 3 methylpyrazole 5 carboxamides


id: cord-023284-i0ecxgus
type: CHEMICAL
entity:
  N substituted 3 methyl 4 diazopyrazole 5 carboxamides and N piperidiny 1 N 1 3 dimethyl 4 nitrosopyrazol 5 yl urea


id: cord-354465-5nqrrnqr
type: CELL_LINE
entity:
  Catalan and Motzkin numbers Characterizations of outerplanar graphs Algorithm independent properties of RNA


id: cord-270587-k56fze59
type: CHEBI
entity:
  Protein carbohydrate complex binding affinity database A Systematic Analysis of Protein Carbohydrate


id: cord-270587-k56fze59
type: ORG
entity:
  Clinic Evaluation of Selected Classical Force Fields for Alchemical Binding Free Energy Calculations of Protein Carbohydrate Complexes Computational


id: cord-270587-k56fze59
type: ORG
entity:
  Glycan Analysis and Synthesis Computational Glycobiology Mechanistic Studies of Carbohydrate Active Enzymes and Implication for Inhibitor Design


id: cord-270587-k56fze59
type: ORG
entity:
  the Conformational Properties of O Linked Glycopeptides Identification of Rare Lewis Oligosaccharide Conformers in Aqueous Solution Using Enhanced Sampling Molecular Dynamics Ring Puckering Landscapes of Glycosaminoglycan


id: cord-270587-k56fze59
type: ORG
entity:
  CHARMM Force Field Files All Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins Extending


id: cord-270587-k56fze59
type: WORK_OF_ART
entity:
  The Effect of Temperature Cations and Number of Acyl Chains on the Lamellar to Non Lamellar Transition


id: cord-270587-k56fze59
type: WORK_OF_ART
entity:
  Flexibility and Explicit Solvent in Molecular Dynamics Based Docking of Protein Glycosaminoglycan Systems Mannobiose Binding Induces Changes in Hydrogen Bonding and Protonation States of Acidic Residues


id: cord-270587-k56fze59
type: WORK_OF_ART
entity:
  An Adjustable Tool for Building 3D Molecular Structures of Carbohydrates for Molecular Simulation Software


id: cord-270587-k56fze59
type: ORG
entity:
  Scoring Functions Conformational Analysis of Oligosaccharides and Polysaccharides Using Molecular Dynamics Simulations A Method for Discretizing and Visualizing Pyranose Conformations


id: cord-270587-k56fze59
type: ORG
entity:
  the Vicinity of Carbohydrate Residues Performed by GlyVicinity Rules of Engagement of Protein Glycoconjugate Interactions


id: cord-270587-k56fze59
type: ORG
entity:
  Molecular Modeling Conformational Studies of Oligosaccharides Structure Conformation and Dynamics of Bioactive Oligosaccharides Theoretical Approaches


id: cord-270587-k56fze59
type: PRODUCT
entity:
  Crystallography NMR System A New Software Suite for Macromolecular Structure Determination Version 1


id: cord-270587-k56fze59
type: ORG
entity:
  the Protein Data Bank A Practical Guide to Using Glycomics Databases Implementation of GlycanBuilder


id: cord-270587-k56fze59
type: ORG
entity:
  Molecular Design Limited Protein Data Bank Contents Guide Atomic Coordinate Entry Format Description


id: cord-257494-242k58ll
type: PROTEIN
entity:
  major histocompatibility complex class I like hereditary hemochromatosis protein HFE transferrin receptor 2


id: cord-257494-242k58ll
type: CL
entity:
  mutans C albicans Eikenella corrodens Actinobacillus actinomycetemcomitans Streptococcus pneumoniae Haemophilus influenzae Streptococcus pyogenes Bacteroides fragilis E coli


id: cord-310847-63gh2tg4
type: PROTEIN
entity:
  Poly L Glutamic Acid and Copolymers of L Glutamic Acid and L Leucine Human matrix metalloproteinases


id: cord-310847-63gh2tg4
type: DISEASE
entity:
  cleft of plant lysozymes 106 Each enzyme in the α amylase family of multidomain hydrolases and transferases has one glutamic acid


id: cord-023208-w99gc5nx
type: PROTEIN
entity:
  crude peptides H Lys Thr Asn Met Lys His Met b Ala Gly b Ala Ala Ala b Ala Gly b Ala Val Val b Gly Gly b Leu Gly OH b 1 b Th120 EFFICIENT


id: cord-023208-w99gc5nx
type: CELL_TYPE
entity:
  blood cells G Bai 1 P Gomes 1 R Seixas 1 M Hicks 2 M Prieto 3 M Bastos 1 Eukaryotic antibiotic peptides


id: cord-023208-w99gc5nx
type: PROTEIN
entity:
  cyclic β2 3 amino acids 1S 2S 1R 2R ACHC and 1S 2S 1R 2R ACPC Low temperature 233 K 1H NMR spectra in CD3OD


id: cord-023208-w99gc5nx
type: PROTEIN
entity:
  N Terminus His Phe Arg and Trp Positions 2 Department of Experimental and Health Sciences Graduate School of Pharmaceutical Sciences 2 Graduate School of Agriculture 3 Graduate School of Medicine


id: cord-023208-w99gc5nx
type: GGP
entity:
  isopropylidenedicyclohexane 4 4 disubstituted bicyclohexane 1 4 disubstituted cyclohexane 1 5 disubstituted cyclooctane and 1 2 1 3


id: cord-023208-w99gc5nx
type: GGP
entity:
  PKA PKC Ca2 channel activators classical regulatory peptides bradykinin somatostatin Met enkephalin endothelin neurotensin


id: cord-023208-w99gc5nx
type: CHEBI
entity:
  amino acid protein stromal cell derived factor 1α SDF 1α 1 One strategy for the treatment of these diseases could be to block the interaction between CXCR4 and SDF 1α with small CXCR4


id: cord-023208-w99gc5nx
type: GGP
entity:
  Tyr 4 SO3H Thr Gln OH II H D Phe 4 SO3H Ile Tyr 4 SO3H Thr Gln OH III H Tyr Ile Tyr 4 SO3H Thr Gln OH IV H Tyr 4 SO3H Ile Tyr Thr Gln OH V


id: cord-023208-w99gc5nx
type: GGP
entity:
  human i e cholic acid CA chenodeoxycholic acid CDCA deoxycholic acid DCA ursodeoxycholic acid UDCA and lithocholic acid


id: cord-023208-w99gc5nx
type: CHEMICAL
entity:
  His Met b Ala Gly b Ala Ala Ala b Ala Gly b Ala Val Val b Gly Gly b Leu Gly OH b 1 b Th120 EFFICIENT


id: cord-023208-w99gc5nx
type: CHEMICAL
entity:
  4 4 disubstituted isopropylidenedicyclohexane 4 4 disubstituted bicyclohexane 1 4 disubstituted cyclohexane 1 5 disubstituted cyclooctane


id: cord-023208-w99gc5nx
type: CHEMICAL
entity:
  dehydropeptides Gly ZPhe AbuPO OMe 2 Gly ZPhe AlaPO OEt 2 Gly ZPhe LeuPO OMe 2 Gly ZPhe ValPO OEt 2 Gly ZPhe


id: cord-023208-w99gc5nx
type: CHEMICAL
entity:
  D β Peptide molecules possess interesting conformational characteristics and biological properties They


id: cord-023225-5quigar4
type: PROTEIN
entity:
  Glycyl tRNA Synthetase S R Stone 1 K Hoffmann 1 2 N Milech 1 2 P T Cunningham 1 M Kerfoot 1 S Winslow 1 Y F Tan 1 M Anastasas 1 C Hall 1 M Scobie 1 P Watt 2 and R Hopkins 1 2 1 Drug Discovery Technology Unit Telethon Institute for Child Health Research 100 Roberts Road Subicao 6008 Western Australia 2 Phylogica Pty Ltd 100 Roberts Road Subiaco 6008 Western Australia Biopanning


id: cord-023225-5quigar4
type: PROTEIN
entity:
  linear covalent structure Ac Aib Asn Leu Aib Pro Ala Val Aib Pro Aib Leu Aib Pro Leuol Ac acetyl Aib


id: cord-023225-5quigar4
type: PROTEIN
entity:
  Leishmania major C Servis H Zalila I Gonzalez L Lozano N Fasel Department of Biochemistry University of Lausanne


id: cord-023225-5quigar4
type: GGP
entity:
  S S Ac Ser ΨH CF3 Pro NHMe and R S Ac Ser Ψ CF3 HPro NHMe 4 Their thermodynamic and kinetic features


id: cord-023225-5quigar4
type: ORG
entity:
  A Girard E Biron Faculty of Pharmacy Université Laval and CHUQ Research Center Quebec Canada Combinatorial


id: cord-023225-5quigar4
type: ORG
entity:
  Haute Normandie PRIMACEN Institute for Medical Research and Innovation IRIB University of Rouen 76821


id: cord-023225-5quigar4
type: CHEMICAL
entity:
  betaamyloid toxicity 1 2 Aggregated βA causes many pathological changes in cultures of mixed neurons and astrocytes such as sporadic cytoplasmic intracellular Ca 2 signal activation of reactive oxygen


id: cord-023225-5quigar4
type: CHEMICAL
entity:
  N terminal extremity 1 probably this insertion on another portion of the peptide provides a change in the conformation of the molecule and its hydrophobic cluster


id: cord-023225-5quigar4
type: CHEMICAL
entity:
  N N isopropylidene derivatives of Ser Thr containing dipeptides 3 We found the reaction of mannopyranosyl trichloroacetimidate


id: cord-004584-bcw90f5b
type: CELL_LINE
entity:
  G361 tumour cell lines Binder S Kolarova H Bajgar R Tomankova K Daskova A Deparment of Medical Biophysics Faculty of Medicine


id: cord-004584-bcw90f5b
type: DNA
entity:
  double helix Pietro Parisse 1 Matteo Castronovo 2 Bojana Lucic 3 Alessandro Vindigni 3 Giacinto Scoles 2 and Loredana Casalis 1 1 Sincrotrone Trieste S C p A Trieste Italy 2 Temple University Philadelphia USA 3 Protein DNA


id: cord-004584-bcw90f5b
type: PROTEIN
entity:
  voltage gated ion channels Zoltan Nusser Institute of Experimental Medicine Hungarian Academy of Sciences Budapest Hungary Voltage gated Na Nav channels


id: cord-004584-bcw90f5b
type: PROTEIN
entity:
  bacterial light harvesting complexes Katia Duquesne 1 Edward O Reilly 2 Cecile Blanchard 1 Alexandra Olaya Castro 2


id: cord-004584-bcw90f5b
type: PROTEIN
entity:
  helical membrane protein Jana Broecker Sebastian Fiedler Sandro Keller Molecular Biophysics University


id: cord-004584-bcw90f5b
type: WORK_OF_ART
entity:
  The diacylglycerolacyltransferase1 DGAT1 is an integral protein from the reticulum endoplasmic membrane that


id: cord-004584-bcw90f5b
type: ORG
entity:
  Department of Medical Physics and Informatics University of Szeged Hungary 2 Department of Experimental Physics University of Szeged Hungary


id: cord-004584-bcw90f5b
type: WORK_OF_ART
entity:
  Applied and Environmental Chemistry University of Szeged Hungary 5 Institute of Biophysics HAS Biological Research Center


id: cord-004584-bcw90f5b
type: ORG
entity:
  Ahmet Yildiz Department of Physics and Department of Molecular and Cell Biology University of California Berkeley CA


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  N 1 2 4 dihydroxyphenylacetyl L asparaginyl N 12 L lysyl 4 8 diaza 1 12 dodecanediamine Dhpa Asn Dada 12Lys


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  human neurotensin receptor 1 Neurotensin NT pGlu 1 Leu 2 Tyr 3 Glu 4 Asn 5 Lys 6 Pro 7 Arg 8 Arg 9 Pro 10 Tyr 11 Ile 12 Leu 13


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  S4 13 PV peptide However transfection mediated by the scrambled peptide was signifi cantly less effi cient than that obtained for the


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  B10234 B10238 peptide dimer B9870 Suim D Arg Arg Pro Hyp Gly Igl Ser D Igl Oic Arg 2 Suim suberimidyl


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  hexapeptides B o c A C P C P O A C P O A C A C P C A C P C A C P C O M e B o c A C P C P O A C A C P C P O A C A C P C A C P C O M e Boc


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  cycilc hexapeptides cyclo L Lys Gly 3 cyclo L Glu Gly 3 cyclo L Lys D Ala 3 cyclo D Glu L Ala 3 cyclo L Trp D Lys 3


id: cord-023209-un2ysc2v
type: GGP
entity:
  neurohypophyseal nonapeptide hormone cycle1 6 H Cys 1 Tyr 2 Phe 3 Gln 4 Asn 5 Cys 6 Pro 7 Arg 8 Gly 9 NH 2


id: cord-023209-un2ysc2v
type: GGP
entity:
  human neurotensin receptor 1 Neurotensin NT pGlu 1 Leu 2 Tyr 3 Glu 4 Asn 5 Lys 6 Pro 7 Arg 8 Arg 9 Pro 10 Tyr 11 Ile


id: cord-023209-un2ysc2v
type: CHEBI
entity:
  proteins nucleophosmin survivin prion and alpha 7 subunit of acetylcholine receptor AChR Nucleophosmin


id: cord-023209-un2ysc2v
type: GGP
entity:
  hexapeptides B o c A C P C P O A C P O A C A C P C A C P C A C P C O M e B o c A C P C P O A C A C P C P O A C A C P C A C P C O M e


id: cord-023209-un2ysc2v
type: ORG
entity:
  Närvänen Ale 1 Equal Contribution 1 University of Kuopio FINLAND 2 University of Helsinki FINLAND Phage


id: cord-023209-un2ysc2v
type: ORG
entity:
  Biochemistry Creighton University Trusova Valeriya Gorbenko Galyna V N Karazin Kharkov National University


id: cord-023209-un2ysc2v
type: CHEMICAL
entity:
  diastereoisomeric cyclic disubstituted amino acids 1S 3S and 1R 3S 1 amino 3 methoxy cyclopentanecarboxylic acid Ac 5 c OM


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  H1 A M Polyanichko 1 H Wieser 2 1 Faculty of Physics Saint Petersburg State University Russia 2 Dept


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  antitumor nonclassical platinum complexes O Vrana V Kohoutkova V Brabec Institute of Biophysics AS CR Královopolská 135 CZ 61265


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  CYP450 L S Goto 2 C O Hokka 1 J F Lima 2 O R Nascimento 2 A P U Araújo 2 1 Grupo de Engenharia Bioquímica UFSCar BR 2


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  Complex I A L Maniero 1 C Bergamini 2 M Bortolus 1 R Fato 2 S Leoni 2 G Lenaz 2 1 Università degli Studi di Padova Padova Italy 2 Università degli studi di Bologna Bologna Italy Complex I NADH Dehydrogenase


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  arXiv 0805 0696v1 S Soria 1 F Quercioli 3 R Mercatelli 3 F Bianco 2 I Cacciari 2 G Righini 2 1 Centro Studi e Ricerche E Fermi P Del Viminale 2 00184 Rome Italy 2


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  plague F1 capsular antigen A Soliakov 1 J R Harris 1 M R Hicks 2 A Rodger 2 R Woody 3 A Watkinson 4 J H Lakey 1 1 Cell


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  membrane proteins C V Kulkarni 3 O Ces 1 S Iwata 2 R H Templer 1 1 Chemical Biology Centre and Department of Chemistry Imperial College London United Kingdom 2 Division of Molecular


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  lambda bacteriophage epigenetic switch L Finzi Physics Department emory University 400 dowman Dr Atlanta GA 30322 USA


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  topoisomerase II activity H Seidel 1 T Klose 2 H Lilie 2 C G Hübner 1 1 Institute of Physics Ratzeburger Allee 160 23538 Lübeck Germany 2 Institute of Biochemistry and Biotechnology Kurt Mothes Str 3 06120 Halle Germany One essential element


id: cord-004534-jqm1hxps
type: DNA
entity:
  human MEF2D gene W Zhou 1 L Ying 2 1 Molecular Medicine National Heart and Lung Institute Imperial College London London SW7 2AZ UK 2 Chemical Biology


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  OmpF channel E Hajjar 1 A Kumar 1 M Winterhalter 2 P Ruggerone 1 M Ceccarelli 1 1 Department of Physics University of Cagliari Italy 2


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  protein N Maghelli 1 V Krstic 2 N Pavin 2 F Julicher 2 I Tolic Norrelykke 1 1 MPI CBG Dresden Germany 2 MPI PKS Dresden Germany


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  integrin αIIbβ3 M Rocco 1 C Rosano 1 J W Weisel 2 D Horita 3 R R Hantgan 3 1 Istituto Nazionale per la Ricerca sul Cancro IST Genova Italy 2


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  redox cofactor L Erokhova 1 P Kügler 2 P Pohl 1 1 Institute of Biophysics Johannes Kepler University Linz Austria 2


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  cation channels Y Sawada 1 M Murase 2 M Sokabe 1 1 Dept Physiol Nagoya Univ Grad Sch Med Nagoya Japan 2


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  Na K ATPase C H Chang 1 T Y Tsong 2 1 Institute of Physics National Chiao Tung university Physics Division National Center for Theoretical Sciences Hsinchu Taiwan 2 Institute of Physics Academy of Sciences Taipei 115 Taiwan Na K ATPase


id: cord-004534-jqm1hxps
type: CELL_TYPE
entity:
  permeabilized skeletal muscle fibres D S Ushakov D Ibanez Garcia T G West P M W French M A Ferenczi Imperial College London UK


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  extracellular matrix molecule hyaluronic acid modulates L type voltage dependent Ca2 channels E Dvoretskova 1 G Kochlamazashvili 2 O Bukalo 2 C Henneberger 3 D Rusakov 3 M Schachner 2 A Dityatev 1 1 Italian Institute of Technology Genova Italy 2


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  colicin translocon C L Johnson 1 A Solovyova 1 P Callow 2 S A Holt 3 L A Clifton 3 K Weiss 4 J H Lakey 1 1


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  human 3 phosphoglycerate kinase P Lallemand 1 J Rouhana 1 L Chaloin 1 B Roy 2 S Arold 3 T Barman 1 C Lionne 1 1 CPBS UMR 5236 4 bd Henri IV


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  Green Fluorescent Protein G Jung Biophysical Chemistry Saarland University 66123 Saarbruecken Germany Biotechnological design of the Green Fluorescent Protein GFP


id: cord-004534-jqm1hxps
type: PROTEIN
entity:
  J Strömqvist 1 S Johansson 1 Y Ohsugi 3 K Andersson 2 L Xu 1 M Kinjo 3 P Höglund 2 J Widengren 1 1 Experimental biomolecular Physics KTH Stockholm Sweden 2


id: cord-004534-jqm1hxps
type: GGP
entity:
  Alzheimer s disease Some diabetes drugs appear to decrease the cognitive decline associated with Alzheimer s


id: cord-004534-jqm1hxps
type: GGP
entity:
  human 3 phosphoglycerate kinase P Lallemand 1 J Rouhana 1 L Chaloin 1 B Roy 2 S Arold 3 T Barman 1 C Lionne 1 1


id: cord-004534-jqm1hxps
type: ORG
entity:
  Institute for Problems of Cryobiology and Cryomedicine National Academy of Sciences of Ukraine Kharkov Ukraine


id: cord-004534-jqm1hxps
type: ORG
entity:
  Physics Department University of Genoa Italy 2 Biochemical Sciences Department University of Florence Italy Short


id: cord-004534-jqm1hxps
type: ORG
entity:
  Molski Adam Mickiewicz University Laboratory for Dynamics of Physicochemical Processes Poznan Poland RNAzymes


id: cord-004534-jqm1hxps
type: ORG
entity:
  Department of Physics Faculty of Science Messina University Italy 2 Department of Physics Faculty of Science Perugia University Italy Important


id: cord-004534-jqm1hxps
type: ORG
entity:
  Chemistry University of Oxford Oxford U K 2 Department of Electronics Computer Science and Systems University of Bologna Bologna Italy Potassium


id: cord-004534-jqm1hxps
type: ORG
entity:
  Institute of Physics National Chiao Tung university Physics Division National Center for Theoretical Sciences Hsinchu


id: cord-004534-jqm1hxps
type: ORG
entity:
  Department of Physics University of Warwick U K 2 Department of Chemistry University of Warwick U K Information


id: cord-004534-jqm1hxps
type: ORG
entity:
  Biotechnology Jagiellonian University 2 Department of Pharmacodynamics Medical College Jagiellonian University


id: cord-004534-jqm1hxps
type: LAW
entity:
  A Isvoran 1 E Quiniou 2 C Craescu 2 L Mouawad 2 1 West University of Timisoara Department of Chemistry Pestalozzi


id: cord-004534-jqm1hxps
type: WORK_OF_ART
entity:
  A Martino D Crane I M Feavers B Bolgiano Division of Bacteriology National Institute for Biological Standards and Control Potters


id: cord-004534-jqm1hxps
type: CHEMICAL
entity:
  E Del Favero 1 G Di Fede 2 F Tagliavini 2 M Salmona 3 L Cantù 1 1 University of Milan Segrate Italy 2 Carlo


id: cord-004534-jqm1hxps
type: CHEMICAL
entity:
  L D Alfonso 1 M Collini 1 M Caccia 1 G Tallarida 2 S Caprioli 2 G Chirico 1 1 Dipartimento di Fisica Università di Milano Bicocca Italy 2 Laboratorio


id: cord-004534-jqm1hxps
type: CHEMICAL
entity:
  1 D Magatti 1 B Cardinali 2 A Profumo 2 M Rocco 2 1 Dipartimento di Fisica e Matematica Università dell Insubria


id: cord-001835-0s7ok4uw
type: PROTEIN
entity:
  villin headpiece miniprotein Stanislaw Oldziej 1 Wioletta _ Zmudzi nska 1 Anna Hałabis 1 1 The C terminal subdomain


id: cord-001835-0s7ok4uw
type: PROTEIN
entity:
  human glucose 6 phosphate dehydrogenase G6PD Nurriza Ab Latif 1 2 Paul Engel 1 1 Conway Institute Univerversity College Dublin 2 Faculty of Biosciences and Medical Engineering Universiti Teknologi Malaysia Human glucose 6 phosphate dehydrogenase G6PD


id: cord-001835-0s7ok4uw
type: PROTEIN
entity:
  coagulation factor VIIa Jais R Bjelke 1 Gorm Andersen 1 Henrik Østergaard 1 Laust B Johnsen 1 Anette A Pedersen 1 Tina H Glue 1 1


id: cord-001835-0s7ok4uw
type: PROTEIN
entity:
  enoyl CoA hydratase family Fernandes 1 Teresa Sorbo 2 Ivan Duka 2 Lia Christina Appold 3 Marianne Ilbert 4 Fabian Kiessling 3 CNRS UMR 7281 5 UCiBio REQUIMTE


id: cord-001835-0s7ok4uw
type: GGP
entity:
  Biryukova 1 Elizaveta Kostanova 1 Alexey Kononikhin 0 Anna Bugrova 1 Evgeny Nikolaev 0 Mark Rosenfeld 1 1 N M


id: cord-001835-0s7ok4uw
type: ORG
entity:
  School of Chemistry National University of Ireland Galway 2 School of Biochemistry and Immunology Trinity College


id: cord-001835-0s7ok4uw
type: WORK_OF_ART
entity:
  Destabilizing the Transient Helical Conformation of Islet Amyloid Polypeptide Hastens Peptide Self Assembly and Potentiates Cytotoxicity Carole Anne de Carufel 1


id: cord-001835-0s7ok4uw
type: EVENT
entity:
  Physical and Engineering Biology Yale University 3 Mechanical Engineering and Materials Science Yale University 4 Applied Physics Yale University


id: cord-001835-0s7ok4uw
type: ORG
entity:
  Department of Biology Stanford University 2 Department of Pediatrics Stanford University 3 Department of Pharmacology University of California San Diego 4 Department of Pediatrics Emory University 5 Institute for Biomedical Sciences


id: cord-001835-0s7ok4uw
type: ORG
entity:
  Graduate School of Science and Engineering Ibaraki University 3 Department of Life Science Graduate School of Life Science University of Hyogo 4


id: cord-001835-0s7ok4uw
type: ORG
entity:
  The New York Structural Biology Center 5 Department of Biochemistry Faculty of Medicine University of Montreal


id: cord-001835-0s7ok4uw
type: ORG
entity:
  University of Southern California Keck School of Medicine 2 Developing a Technique to Detect Deamidated Proteins


id: cord-001835-0s7ok4uw
type: ORG
entity:
  the Ethical Committee for Animal Experimentation from Center of Health and Science of the Federal University of Rio de Janeiro


id: cord-001835-0s7ok4uw
type: ORG
entity:
  1 National Autonomous University of Mexico Faculty of Medicine 2 National Autonomous University of Mexico Faculty of Chemistry 3


id: cord-001835-0s7ok4uw
type: WORK_OF_ART
entity:
  Deartment of Biology Wilfrid Laurier University 2 Department of Biology University of Waterloo Chloroplast


id: cord-001835-0s7ok4uw
type: ORG
entity:
  University of Greenwich Faculty of Engineering and Sciene 2 University of Greenwich Centre of Sports Science and Human Performance


id: cord-001835-0s7ok4uw
type: CHEMICAL
entity:
  N terminal recognition element In addition expressed protein ligation is being used to incorporate backbone modifications such as the thioamide


id: cord-001835-0s7ok4uw
type: CHEMICAL
entity:
  N terminal catalytic module 2 This module shows the capacity of recognize the GlcNAc MurNAc L Ala D isoGln muropeptide GMDP


id: cord-001835-0s7ok4uw
type: DISEASE
entity:
  acute myeloid leukemia mutations Daniela Marasco 1 Concetta Di Natale 1 Valentina Punzo 1 Domenico Riccardi 1 Pasqualina Scognamiglio 1 Roberta Cascella 2 Cristina Cecchi 2 Fabrizio Chiti 2 Marilisa Leone


id: cord-001835-0s7ok4uw
type: DISEASE
entity:
  human immunodeficiency virus type 1 subtype C based on Envelope V3 sequences Available http istree bioprotection org Signal processing based Bioinformatics methods


# bib

id: cord-000822-iuglkdcp
title: Predicting pseudoknotted structures across two RNA sequences
author: Sperschneider, Jana
date: 2012-12-01
txt: ./txt/cord-000822-iuglkdcp.txt
cache: ./cache/cord-000822-iuglkdcp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516145/
doi: 10.1093/bioinformatics/bts575
summary:
  One strong point of the DotKnot method for single sequence pseudoknot prediction (Sperschneider and Datta, 2010; Sperschneider et al., 2011) is that the set of possible H-type pseudoknot candidates (and secondary structure elements) is explicitly computed and thus readily available for further investigation. (3) Use significant pairs to calculate the set of conserved structure elements and pseudoknots for the two sequences that maximizes a combined free energy and similarity score. The key point of the DotKnot-PW approach is how to score the similarity of stems, secondary structure elements and H-type pseudoknot candidates derived from sequences Seq x and Seq y . The optimal structure element alignment, which preserves the interval ordering includes structure elements p 1 , p 4 , p 7 in the first sequence and p 1 , p 4 , p 6 in the second sequence pairwise prediction with highest combined free energy and similarity score is taken, DotKnot-PW has an improved average MCC of 0.81.

abstract:
  Motivation: Laboratory RNA structure determination is demanding and costly and thus, computational structure prediction is an important task. Single sequence methods for RNA secondary structure prediction are limited by the accuracy of the underlying folding model, if a structure is supported by a family of evolutionarily related sequences, one can be more confident that the prediction is accurate. RNA pseudoknots are functional elements, which have highly conserved structures. However, few comparative structure prediction methods can handle pseudoknots due to the computational complexity. Results: A comparative pseudoknot prediction method called DotKnot-PW is introduced based on structural comparison of secondary structure elements and H-type pseudoknot candidates. DotKnot-PW outperforms other methods from the literature on a hand-curated test set of RNA structures with experimental support. Availability: DotKnot-PW and the RNA structure test set are available at the web site http://dotknot.csse.uwa.edu.au/pw. Contact: janaspe@csse.uwa.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.


id: cord-001835-0s7ok4uw
title: Abstracts of the 29th Annual Symposium of The Protein Society
author: nan
date: 2015-10-01
txt: ./txt/cord-001835-0s7ok4uw.txt
cache: ./cache/cord-001835-0s7ok4uw.txt
extension: .txt
mime: text/plain
url: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pro.2823
doi: 10.1002/pro.2823
abstract: nan
summary:
  Altogether, these results indicate that, although PHDs might be more selective for HIF as a substrate as it was initially thought, the enzymatic activity of the prolyl hydroxylases is possibly influenced by a number of other proteins that can directly bind to PHDs. Non-natural aminoacids via the MIO-enzyme toolkit Alina Filip 1 , Judith H Bartha-V ari 1 , Gergely B an oczy 2 , L aszl o Poppe 2 , Csaba Paizs 1 , Florin-Dan Irimie 1 1 Biocatalysis and Biotransformation Research Group, Department of Chemistry, UBB, 2 Department of Organic Chemistry and Technology An attractive enzymatic route to enantiomerically pure to the highly valuable a-or b-aromatic amino acids involves the use of aromatic ammonia lyases (ALs) and aminomutases (AMs). Continuing our studies of the effect of like-charged residues on protein-folding mechanisms, in this work, we investigated, by means of NMR spectroscopy and molecular-dynamics simulations, two short fragments of the human Pin1 WW domain [hPin1(14-24); hPin1(15-23)] and one single point mutation system derived from hPin1(14-24) in which the original charged residues were replaced with non-polar alanine residues.


id: cord-002015-s3tdllby
title: The elusive quest for RNA knots
author: Burton, Aaron S.
date: 2016-02-01
txt: ./txt/cord-002015-s3tdllby.txt
cache: ./cache/cord-002015-s3tdllby.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829277/
doi: 10.1080/15476286.2015.1132069
summary:
  2, 3 It is therefore a remarkable fact that the statistical incidence of topological entanglement in biomolecules such as proteins and DNA filaments, which are both long and compact, is substantially smaller than expected for general models of equilibrated polymers with equivalent length and packing conditions. It is accordingly plausible, as remarked by Levinthal in more general contexts, 7,8 that protein sequences have evolved to encode not only the thermodynamically-stable native fold, but also the sequence of steps leading to the native structure formation so to minimize the incidence of misfolded states, including knotted ones which would be very challenging to backtrack. It is possible that the sequence of naturally-occurring RNAs, some of which need to be efficiently translocated through biological pores, have evolved to harness folding kinetics and thermodynamics so as to minimize the incidence of various forms of selfentanglement, including knots, in their native structures.

abstract:
  Physical entanglement, and particularly knots arise spontaneously in equilibrated polymers that are sufficiently long and densely packed. Biopolymers are no exceptions: knots have long been known to occur in proteins as well as in encapsidated viral DNA. The rapidly growing number of RNA structures has recently made it possible to investigate the incidence of physical knots in this type of biomolecule, too. Strikingly, no knots have been found to date in the known RNA structures. In this Point of View Article we discuss the absence of knots in currently available RNAs and consider the reasons why knots in RNA have not yet been found, despite the expectation that they should exist in Nature. We conclude by singling out a number of RNA sequences that, based on the properties of their predicted secondary structures, are good candidates for knotted RNAs.


id: cord-002490-kw8psrmz
title: Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 Å resolution
author: Beniac, Daniel R.
date: 2017-04-11
txt: ./txt/cord-002490-kw8psrmz.txt
cache: ./cache/cord-002490-kw8psrmz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387728/
doi: 10.1038/srep46374
summary:
  We present the structure of the surface Ebola virus (EBOV) trimeric glycoprotein (GP) spike at 11 Å resolution, in situ within the viral plasma membrane of purified virus particles. In addition, 29,976 images were selected for reference-free analysis of the half-diameter of EBOV to investigate the spatial distribution of the GP spikes, as well as the periodicity and symmetrical relationships between GP and the matrix protein VP40 in the envelope, and the underlying nucleocapsid layer (Figs 1c and S3) . The spike structure of Beniac et al imaged within the virus-like particles was somehow clipped, since this should have included the mucin-like domains: in addition, tomography was combined with single-particle analysis, which may have distorted the results 4 . The structure that we report here is based entirely on the well-accepted method of single-particle analysis using projection matching, and is broadly similar to that published of expressed GP in virus-like particles using tomography 28, 29 : there are noticeable differences in shape and size of the spike, as well as in resolution (Fig. 4) .

abstract:
  We present the structure of the surface Ebola virus (EBOV) trimeric glycoprotein (GP) spike at 11 Å resolution, in situ within the viral plasma membrane of purified virus particles. GP functions in cellular attachment, endosomal entry, and membrane fusion to initiate infection, and is a key therapeutic target. Nevertheless, only about half of the GP molecule has yet been solved to atomic resolution, excluding the mucin-like and transmembrane domains, and some of the glycans. Fitting of the atomic resolution X-ray data from expressed, truncated deletion constructs within our 11 Å structure of the entire molecule demonstrates the relationship between the GP1-GP2 domains, the mucin-like and transmembrane domains, and the bilaminar lipid envelope. We show that the mucin-like domain covers the glycan cap and partially occludes the receptor binding sites prior to proteolytic cleavage. Our structure is also consistent with key antibody neutralisation sites on GP being accessible prior to proteolysis. Based on the findings of us and others, GP-mediated binding may create an angle of 18 degrees between the planes of viral and endosomal membranes.


id: cord-003020-q69f57el
title: Computer-aided design of amino acid-based therapeutics: a review
author: Farhadi, Tayebeh
date: 2018-05-14
txt: ./txt/cord-003020-q69f57el.txt
cache: ./cache/cord-003020-q69f57el.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958949/
doi: 10.2147/dddt.s159767
summary:
  Computational techniques play a key role to design and develop the amino acid-based therapeutics such as proteins, peptides and peptidomimetics. Here, the elaborated techniques that are developed to characterize the amino acid sequences consistent with a specific structure and allow protein design are discussed. 3 Recently, pharmaceutical scientists have shown interest in engineering amino acid-based therapeutics such as proteins, peptides and peptidomimetics. Computer-aided design of amino acid-based therapeutics Fixing the backbone decreases the computational complication, but it may inhibit the main chain modifications to adjust sequence alternation. Computer-aided design of amino acid-based therapeutics to model peptide binding to targets of interest. 28, 134 Sequence-based method Recently, a method has been developed to rank peptide compound matches that are limited to short linear motifs in proteins and compounds with amino acid substituents.

abstract:
  During the last two decades, the pharmaceutical industry has progressed from detecting small molecules to designing biologic-based therapeutics. Amino acid-based drugs are a group of biologic-based therapeutics that can effectively combat the diseases caused by drug resistance or molecular deficiency. Computational techniques play a key role to design and develop the amino acid-based therapeutics such as proteins, peptides and peptidomimetics. In this study, it was attempted to discuss the various elements for computational design of amino acid-based therapeutics. Protein design seeks to identify the properties of amino acid sequences that fold to predetermined structures with desirable structural and functional characteristics. Peptide drugs occupy a middle space between proteins and small molecules and it is hoped that they can target “undruggable” intracellular protein–protein interactions. Peptidomimetics, the compounds that mimic the biologic characteristics of peptides, present refined pharmacokinetic properties compared to the original peptides. Here, the elaborated techniques that are developed to characterize the amino acid sequences consistent with a specific structure and allow protein design are discussed. Moreover, the key principles and recent advances in currently introduced computational techniques for rational peptide design are spotlighted. The most advanced computational techniques developed to design novel peptidomimetics are also summarized.


id: cord-004534-jqm1hxps
title: Abstract
author: nan
date: 2009-06-09
txt: ./txt/cord-004534-jqm1hxps.txt
cache: ./cache/cord-004534-jqm1hxps.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079852/
doi: 10.1007/s00249-009-0478-1
abstract: nan
summary:
  HIV-1 to efficiently complete a replication cycle has to integrate its genome into the host cellular DNA.After HIV-1 enters target cells,neosynthesized viral DNA forms along with other proteins the pre-integration complex (PIC).PICs are then transported into the nucleus where integration,catalyzed by the viral integrase,takes place.HIV-1 viral particles engineered to incorporate integrase fused to EGFP have proven effective to study PICs within nuclei of infected cells.In this study we report the live imaging analysis of nuclear PIC dynamics obtained by time-lapse microscopy.Intranuclear trajectories of IN-EGFP-labeled PIC were collected in three dimensions and examined by both mean squared displacement (MSD) and cage diameter (CD) analysis.In CD the maximum distances measured between two positions occupied by a PIC in a time window of 2 minutes were calculated while in our MSD analysis 5-minute long trajectory segments were considered.Remarkably,MSD revealed the presence of an underlying active transport mechanism.To test the possible role of actin filaments,PIC nuclear trafficking was analyzed in cells treated with latrunculin B (actin polymerization inhibitor).Preliminary results suggest that the disruption of actin function impairs the active nuclear movement of PICs. Second harmonic generation microscopy reveals sarcomere contractile dynamics of cardiomyocytes N.


id: cord-007373-livz5zuu
author: Gayathri, P.
date: 2006-03-15
txt: ./txt/cord-007373-livz5zuu.txt
cache: ./cache/cord-007373-livz5zuu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111806/
doi: 10.1016/j.virol.2005.11.011
summary:
  authors: Gayathri, P.; Satheshkumar, P.S.; Prasad, K.; Nair, Smita; Savithri, H.S.; Murthy, M.R.N. title: Crystal structure of the serine protease domain of Sesbania mosaic virus polyprotein and mutational analysis of residues forming the S1-binding pocket In the present study, the crystal structure of SeMV protease domain was determined to a resolution of 2.4 Å by multiple isomorphous replacement coupled with anomalous scattering, with a view to identify the residues involved in substrate binding as well as protease -VPg interactions. The absence of well-defined density for F301 in SeMV protease suggests that its side chain might undergo substantial displacement on binding of the substrate or on conformational changes induced by the interaction of the protease domain with VPg. TEV and equine arteritis virus proteases, in which a serine residue occurs at the position corresponding to F301, are active in trans.

title:
  Crystal structure of the serine protease domain of Sesbania mosaic virus polyprotein and mutational analysis of residues forming the S1-binding pocket

abstract:
  Sesbania mosaic virus (SeMV) polyprotein is processed by its N-terminal serine protease domain. The crystal structure of the protease domain was determined to a resolution of 2.4 Å using multiple isomorphous replacement and anomalous scattering. The SeMV protease domain exhibited the characteristic trypsin fold and was found to be closer to cellular serine proteases than to other viral proteases. The residues of the S1-binding pocket, H298, T279 and N308 were mutated to alanine in the ΔN70-Protease–VPg polyprotein, and the cis-cleavage activity was examined. The H298A and T279A mutants were inactive, while the N308A mutant was partially active, suggesting that the interactions of H298 and T279 with P1-glutamate are crucial for the E–T/S cleavage. A region of exposed aromatic amino acids, probably essential for interaction with VPg, was identified on the protease domain, and this interaction could play a major role in modulating the function of the protease.


id: cord-008588-4eu9v5d3
title: Structural Elements in RNA
author: Chastain, Michael
date: 2008-02-29
txt: ./txt/cord-008588-4eu9v5d3.txt
cache: ./cache/cord-008588-4eu9v5d3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133162/
doi: 10.1016/s0079-6603(08)60008-2
summary:
  The structures of the tRNA anticodon loop and the UUCG loop suggest that the specific loop sequences adopt conformations that are more stable because they contain more hydrogen bonding and stacking interactions-particularly interactions with the sugar-phosphate backbone. Determining the conformation of these loops in RNA is important for understanding how these nucleotides interact with other elements of secondary structure to form tertiary interactions and for understanding how proteins bind to bulge loops. In general, this could occur between any of the secondary structure regions containing unpaired nucleotides (single-stranded regions, hairpin loops, bulge loops, internal loops, and junction loops). There are several examples of RNA molecules containing tertiary contacts between nucleotides that are in loop regions of secondary structure. The high frequency with which known RNA structures contain tertiary pairing between nucleotides that are unpaired in the secondary structure stresses the importance of learning more about such interactions.

abstract:
  This chapter describes the RNA structural characteristics that have emerged so far. Folded RNA molecules are stabilized by a variety of interactions, the most prevalent of which are stacking and hydrogen bonding between bases. Many interactions among backbone atoms also occur in the structure of tRNA, although they are often ignored when considering RNA structure because they are not as well-characterized as interactions among bases. Backbone interactions include hydrogen bonding and the stacking of sugar or phosphate groups with bases or with other sugar and phosphate groups. The interactions found in a three-dimensional RNA structure can be divided into two categories: secondary interactions and tertiary interactions. This division is useful for several reasons. Secondary structures are routinely determined by a combination of techniques discussed in chapter, whereas tertiary interactions are more difficult to determine. Computer algorithms that generate RNA structures can search completely through possible secondary structures, but the inclusion of tertiary interactions makes a complete search of possible structures impractical for RNA molecules even as small as tRNA. The division of RNA structure into building blocks consisting of secondary or tertiary interactions makes it easier to describe RNA structures. In those cases in which RNA studies are incomplete, the studies of DNA are described with the rationalization that RNA structures may be analogous to DNA structures, or that the techniques used to study DNA could be applied to the analogous RNA structures. The chapter focuses on the aspects of RNA structure that affect the three-dimensional shape of RNA and that affect its ability to interact with other molecules.


id: cord-009660-23cdi61w
title: Electron microscopic observations on structures resembling myxovirus in human sarcomas
author: Györkey, Ferenc
date: 2006-06-27
txt: ./txt/cord-009660-23cdi61w.txt
cache: ./cache/cord-009660-23cdi61w.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162171/
doi: 10.1002/1097-0142(197106)27:6<1449::aid-cncr2820270627>3.0.co;2-3
summary:
  Herpes, adeno-and reoviruses, as well as elementary bodies of mycoplasma, occasionally occur in human tumors probably as passengers and not -~ as etiologically important agents.1~8~20 Occasionally, type C and related virus-like particles were found in neoplastic tissues deriving from human leukemia, lymphoma, and sarcoma.8J6 T h e number of these particles rapidly diminishes in cells cultured in vitro; thus, these viruslike particles have never been identified as the human counterparts of oncogenic type C viruses of animals. Preliminary findings concerning such structures, however, have recently been reported by Stewart36 who observed the occurrence of filamentous structures and budding type Clike virus particles in tissue cultures of human liposarcoma and Hodgkin''s disease. T h e present paper is a preliminary report on morphological observations concerning structures that may be of viral derivation, as found in biopsies and tissue cultures of human tumors of mesenchymal origin.

abstract:
  Human tumors of mesenchymal origin contain cytoplasmic structures resembling ribonucleoprotein strands of paramyxoviruses. Similar structures have previously been reported in collagen diseases. The nature and function of these structures remain unresolved.


id: cord-010260-8lnpujip
title: The blind watchmaker and rational protein engineering
author: Anthonsen, Henrik W.
date: 1994-08-31
txt: ./txt/cord-010260-8lnpujip.txt
cache: ./cache/cord-010260-8lnpujip.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173218/
doi: 10.1016/0168-1656(94)90152-x
summary:
  In the present review some scientific areas of key importance for protein engineering are discussed, such as problems involved in deducting protein sequence from DNA sequence (due to posttranscriptional editing, splicing and posttranslational modifications), modelling of protein structures by homology, NMR of large proteins (including probing the molecular surface with relaxation agents), simulation of protein structures by molecular dynamics and simulation of electrostatic effects in proteins (including pH-dependent effects). In the present review we will look at the design part of the protein engineering process, with emphasis on some of the more difficult steps, especially homology based modelling in cases with very low sequence similarity, nuclear magnetic resonance (NMR) of very large proteins and modelling of electrostatic interactions. They modify properties of individual residues and of the protein, and may thus make surface prediction, dynamics simulations and structural modelling in general more complex.

abstract:
  In the present review some scientific areas of key importance for protein engineering are discussed, such as problems involved in deducting protein sequence from DNA sequence (due to posttranscriptional editing, splicing and posttranslational modifications), modelling of protein structures by homology, NMR of large proteins (including probing the molecular surface with relaxation agents), simulation of protein structures by molecular dynamics and simulation of electrostatic effects in proteins (including pH-dependent effects). It is argued that all of these areas could be of key importance in most protein engineering projects, because they give access to increased and often unique information. In the last part of the review some potential areas for future applications of protein engineering approaches are discussed, such as non-conventional media, de novo design and nanotechnology.


id: cord-013387-q91052qw
title: Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach
author: Leão, Rozires P.
date: 2020-08-26
txt: ./txt/cord-013387-q91052qw.txt
cache: ./cache/cord-013387-q91052qw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559105/
doi: 10.3390/ph13090209
summary:
  In this initial stage, the pivot molecule rofecoxib was used as a research model for the virtual screening in six commercial molecule databases: Chembridge DIVERSetEXP, DIVERSet CORE Library (https://www.chembridge.com) [24] , Maybridge Collections (www.maybridge.com) [25, 26] , ZINC Drug Database, ZINC Natural Stock (http://zinc.docking.org) [27] , and Drug FDA BindingDB (http://www.bindingdb.org) [27] using the programs Rapid Overlay of Chemical Structures (ROCS) and electrostatic similarity (EON). The bioactivity scores of the LMQC72, LMQC36, and LMQC50 structures were calculated for different parameters, as receptor binding of the ligand to the G protein coupled (GPCR) and nuclear receptor ligand, modulating ion channel, kinase inhibition, protease inhibition, and inhibition of enzyme activity. The bioactivity scores of the LMQC72, LMQC36, and LMQC50 structures were calculated for different parameters, as receptor binding of the ligand to the G protein coupled (GPCR) and nuclear receptor ligand, modulating ion channel, kinase inhibition, protease inhibition, and inhibition of enzyme activity.

abstract:
  The cyclooxygenase-2 receptor is a therapeutic target for planning potential drugs with anti-inflammatory activity. The selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was selected as a pivot molecule to perform virtual ligand-based screening from six commercial databases. We performed the search for similarly shaped Rapid Overlay of Chemical Structures (ROCS) and electrostatic (EON) compounds. After, we used pharmacokinetic and toxicological parameters to determine the best potential compounds, obtained through the softwares QikProp and Derek, respectively. Then, the compounds proceeded to the molecular anchorage study, which showed promising results of binding affinity with the hCOX-2 receptor: LMQC72 (∆G = −11.0 kcal/mol), LMQC36 (∆G = −10.6 kcal/mol), and LMQC50 (∆G = −10.2 kcal/mol). LMQC72 and LMQC36 showed higher binding affinity compared to rofecoxib (∆G = −10.4 kcal/mol). Finally, molecular dynamics (MD) simulations were used to evaluate the interaction of the compounds with the target hCOX-2 during 150 ns. In all MD simulation trajectories, the ligands remained interacting with the protein until the end of the simulation. The compounds were also complexing with hCOX-2 favorably. The compounds obtained the following affinity energy values: rofecoxib: ΔGbind = −45.31 kcal/mol; LMQC72: ΔGbind = −38.58 kcal/mol; LMQC36: ΔGbind = −36.10 kcal/mol; and LMQC50: ΔGbind = −39.40 kcal/mol. The selected LMQC72, LMQC50, and LMQC36 structures showed satisfactory pharmacokinetic results related to absorption and distribution. The toxicological predictions of these compounds did not display alerts for possible toxic groups and lower risk of cardiotoxicity compared to rofecoxib. Therefore, future in vitro and in vivo studies are needed to confirm the anti-inflammatory potential of the compounds selected here with bioinformatics approaches based on rofecoxib ligand.


id: cord-014685-ihh30q6f
title: Posters P788 - P999
author: nan
date: 2005-09-21
txt: ./txt/cord-014685-ihh30q6f.txt
cache: ./cache/cord-014685-ihh30q6f.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080055/
doi: 10.1007/s00249-005-0504-x
abstract: nan
summary:
  This study has attempted to analyse the structural properties of membrane peptides and proteins through the use of model systems that have been designed to mimic their natural counterparts: Podlubnaya 2 1 Institute of Theoretical and Experimental Biophysics RAS, 2 Pushchino State University Amyloid brils are formed by proteins or their peptides in the result of a conformational transition from alpha helix into beta-sheet structure. Analysis of the results of such studies indicate that folding of SNase fragments is dominated by developing the local and non-local nucleation sites from native-like secondary structures and by intensifying the longrange interactions of residues at nucleation sites with residues further removed in sequence. The results show that at different pH values the aggregation processes of both proteins follow different pathways determined by the variations in the native structure and by the details of the involved conformational changes.


id: cord-015619-msicix98
title: Virus Structure & Assembly
author: nan
date: 2009-02-24
txt: ./txt/cord-015619-msicix98.txt
cache: ./cache/cord-015619-msicix98.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111173/
doi: 10.1016/s0006-3495(08)79065-9
abstract: nan
summary:
  The studies were performed with nanoindentation techniques using an Atomic Force Microscope (AFM), an approach which is becoming a standard method to measure the mechanical properties of viral particles (1, 2) . Using molecular dynamics simulations of the connector in complex with DNA, and aiming at distinguishing between these three models, we calculated mechanical properties of this system. The bacteriophage lambda is composed of an icosahedral capsid, into which a 48.5 kbp double-stranded DNA genome is packaged, and a long non-contractile tail consisting of 34 disk-like structures. The relative probabilities of fusion and endocytosis of a virus particle initially nonspecifically adsorbed on the host cell membrane are computed as functions of receptor concentration, binding strength, and number of spikes. As revealed by techniques of structural biology and single-molecule experimentation, the capsids of viruses are some of nature''s best examples of highly symmetric multiscale self-assembled structures with impressive mechanical properties of strength and elasticity.


id: cord-015642-p46abodr
title: Distribution of Graph-Distances in Boltzmann Ensembles of RNA Secondary Structures
author: Backofen, Rolf
date: 2013
txt: ./txt/cord-015642-p46abodr.txt
cache: ./cache/cord-015642-p46abodr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114971/
doi: 10.1007/978-3-642-40453-5_10
summary:
  On a more technical level, the problem to compute the partition function over RNA secondary structures with given end-to-end distance d, usually measured as the number of external bases (plus possibly the number of structural domains) arises for instance when predicting nucleic acid secondary structure in the presence of single-stranded binding proteins [9] or in models of RNA subjected to pulling forces (e.g. in atom force microscopy or export through a small pore) [10, 23, 11] . can be split as follows, This gives the recursion [10] , the investigate of loop entropy dependence [7] , the analysis of FRET signals in the presence of single-stranded binding proteins [9] , as well as in mathematical studies of RNA panhandle-like structures [2, 13] . As the graph-distance for a pair of nucleotides in a given secondary structure can be computed in O(n log n) time, even large samples can be evaluated efficiently 2 . The equilibrium partition function and base pair binding probabilities for RNA secondary structure

abstract:
  Large RNA molecules often carry multiple functional domains whose spatial arrangement is an important determinant of their function. Pre-mRNA splicing, furthermore, relies on the spatial proximity of the splice junctions that can be separated by very long introns. Similar effects appear in the processing of RNA virus genomes. Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium therefore provides useful information on the overall shape of the molecule can provide insights into the interplay of its functional domains. Spatial distance can be approximated by the graph-distance in RNA secondary structure. We show here that the equilibrium distribution of graph-distances between arbitrary nucleotides can be computed in polynomial time by means of dynamic programming. A naive implementation would yield recursions with a very high time complexity of O(n (11)). Although we were able to reduce this to O(n (6)) for many practical applications a further reduction seems difficult. We conclude, therefore, that sampling approaches, which are much easier to implement, are also theoretically favorable for most real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules.


id: cord-017181-ywz6w2po
title: Component-Based Modelling of RNA Structure Folding
author: Maus, Carsten
date: 2008
txt: ./txt/cord-017181-ywz6w2po.txt
cache: ./cache/cord-017181-ywz6w2po.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121681/
doi: 10.1007/978-3-540-88562-7_8
summary:
  As this regulating process depends largely on structure formation, modelling of RNA folding would be a big step in the right direction for reflecting attenuation dynamics. Additionally, modelling interactions between mRNA and RNAP as well as mRNA and the ribosome are needed because both influence the kinetic folding process and RNA termination structures break up gene transcription. If observed structures are present during folding simulation, the macro level model can signalise this information and thus trigger dynamics to other components by adding new ports to itself (representing docking sites) or send messages over existing ports. Simulating the RNA folding with Kinfold [12] results in a five times higher amount of the 2-helix conformation than the single hairpin, but their total sum is about 60% of all molecules and thus less misfolded structures can be observed. The pattern observation function of the RNA folding model, which is realised at macro level, allows us to look for an intrinsic transcription termination structure [2] during simulation.

abstract:
  RNA structure is fundamentally important for many biological processes. In the past decades, diverse structure prediction algorithms and tools were developed but due to missing descriptions in clearly defined modelling formalisms it’s difficult or even impossible to integrate them into larger system models. We present an RNA secondary structure folding model described in ml-Devs, a variant of the Devs formalism, which enables the hierarchical combination with other model components like RNA binding proteins. An example of transcriptional attenuation will be given where model components of RNA polymerase, the folding RNA molecule, and the translating ribosome play together in a composed dynamic model.


id: cord-018133-2otxft31
title: Bioinformatics
author: Altman, Russ B.
date: 2006
txt: ./txt/cord-018133-2otxft31.txt
cache: ./cache/cord-018133-2otxft31.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122933/
doi: 10.1007/0-387-36278-9_22
summary:
  Experimentation and bioinformatics have divided the research into several areas, and the largest are: (1) genome and protein sequence analysis, (2) macromolecular structure-function analysis, (3) gene expression analysis, and (4) proteomics. With the completion of the human genome and the abundance of sequence, structural, and gene expression data, a new field of systems biology that tries to understand how proteins and genes interact at a cellular level is emerging. The Entrez system from the National Center for Biological Information (NCBI) gives integrated access to the biomedical literature, protein, and nucleic acid sequences, macromolecular and small molecular structures, and genome project links (including both the Human Genome Project and sequencing projects that are attempting to determine the genome sequences for organisms that are either human pathogens or important experimental model organisms) in a manner that takes advantages of either explicit or computed links between these data resources.

abstract:
  Why is sequence, structure, and biological pathway information relevant to medicine? Where on the Internet should you look for a DNA sequence, a protein sequence, or a protein structure? What are two problems encountered in analyzing biological sequence, structure, and function? How has the age of genomics changed the landscape of bioinformatics? What two changes should we anticipate in the medical record as a result of these new information sources? What are two computational challenges in bioinformatics for the future?


id: cord-018401-josb16pi
title: Hierarchical Self-Assembled Peptide Nano-ensembles
author: Kumaraswamy, Priyadharshini
date: 2014-03-01
txt: ./txt/cord-018401-josb16pi.txt
cache: ./cache/cord-018401-josb16pi.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123264/
doi: 10.1007/978-3-642-31107-9_23
summary:
  Since peptide self-assembly is a bottom-up process where amino acids form the building blocks, it is easy to introduce functionalities on the carboxyl or amine terminal groups, opening up the possibilities of a wide range of chemical interactions leading to specific functions. These cyclic peptides have alternating D-and L-amino acids, which interact through intermolecular hydrogen bonding to form an array of self-assembled nanotubes with an internal diameter of 7-8 Å (Fig. 8.5 ). Peptide amphiphiles comprise of a hydrophilic head and hydrophobic tail that self-assemble in aqueous solution to form well-defined nanostructures like peptide bilayers, micelles, nanotubes, nanorods, and nanovesicles [64] [65] [66] . The topography of the self-assembled structures formed by two amphiphilic peptidolipids derived from the 31-35 residues of the amyloid beta peptide (C 18 -IIGLM-OH and C 18 -IIGLM-NH 2 ) was observed using this technique [99] .

abstract:
  A variety of peptides can be self-assembled, i.e. self-organized spontaneously, into large and complex hierarchical structures, reproducibly by regulating a range of parameters that can be environment driven, process driven, or peptide driven. These supramolecular peptide aggregates yield different shapes and structures like nanofibers, nanotubes, nanobelts, nanowires, nanotapes, and micelles. These peptide nanostructures represent a category of materials that bridge biotechnology and nanotechnology and are found suitable not only for biomedical applications such as tissue engineering and drug delivery but also in nanoelectronics.


id: cord-018963-2lia97db
title: Protein Structure Prediction by Protein Threading
author: Xu, Ying
date: 2010-04-29
txt: ./txt/cord-018963-2lia97db.txt
cache: ./cache/cord-018963-2lia97db.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123984/
doi: 10.1007/978-0-387-68825-1_1
summary:
  Their follow-up work (Elofsson et aI., 1996; Fischer and Eisenberg, 1996; Fischer et aI., 1996a,b) and the work by Jones, Taylor, and Thornton (Jones et aI., 1992) on protein fold recognition led to the development of a new brand ofpowerful tools for protein structure prediction, which we now term "protein threading." These computational tools have played a key role in extending the utility of all the experimentally solved structures by X-ray crystallography and nuclear magnetic resonance (NMR), providing structural models and functional predictions for many ofthe proteins encoded in the hundreds of genomes that have been sequenced up to now.

abstract:
  The seminal work of Bowie, Lüthy, and Eisenberg (Bowie et al., 1991) on “the inverse protein folding problem” laid the foundation of protein structure prediction by protein threading. By using simple measures for fitness of different amino acid types to local structural environments defined in terms of solvent accessibility and protein secondary structure, the authors derived a simple and yet profoundly novel approach to assessing if a protein sequence fits well with a given protein structural fold. Their follow-up work (Elofsson et al., 1996; Fischer and Eisenberg, 1996; Fischer et al., 1996a,b) and the work by Jones, Taylor, and Thornton (Jones et al., 1992) on protein fold recognition led to the development of a new brand of powerful tools for protein structure prediction, which we now term “protein threading.” These computational tools have played a key role in extending the utility of all the experimentally solved structures by X-ray crystallography and nuclear magnetic resonance (NMR), providing structural models and functional predictions for many of the proteins encoded in the hundreds of genomes that have been sequenced up to now.


id: cord-022494-d66rz6dc
title: Comparative Modeling of Drug Target Proteins
author: Webb, B.
date: 2014-10-01
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157477/
doi: 10.1016/b978-0-12-409547-2.11133-3
abstract:
  In this perspective, we begin by describing the comparative protein structure modeling technique and the accuracy of the corresponding models. We then discuss the significant role that comparative prediction plays in drug discovery. We focus on virtual ligand screening against comparative models and illustrate the state-of-the-art by a number of specific examples.


id: cord-023208-w99gc5nx
title: Poster Presentation Abstracts
author: nan
date: 2006-09-01
txt: ./txt/cord-023208-w99gc5nx.txt
cache: ./cache/cord-023208-w99gc5nx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167816/
doi: 10.1002/psc.797
abstract: nan
summary:
  In order to develop a synthetic protocol by an automated instrumentation, increasing yield, purity of the crude, and reaction time, a microwave-assisted solid phase peptide synthesis was validated comparing the use of the new generation of Triazine-Based Coupling Reagents (TBCRs) with a series of commonly used ones. Ubiquitinium is a well known mechanism in protein degredation of Eukaryotic cells ,in which many obsolte and corrupted three dimentional structure protein ,become marked by covalent attachment of ubuquitin through a multi-step enzymatic pathway.Ubiquitin is a small ,8.5 kDa peptide of 76 amino acid residues that targets such substrtes for proteolysis in proteasome .Recnt studies showed that an extra cellular ubiquitination process also taking place in the epididymes of humans and other animals marks protein on the surface of the defective sperm .it appears that structurally and functionally defective sperm become surface ubiquitinated by epididymal epithelial cells. This head-to-tailcyclized 14-amino-acid peptide contains one disulfide bridge and a lysine residue (Lys5) present in the P1 position, which is responsible for inhibitor specificity.As was reported by us and other groups, SFTI-1 analogues with one cycle only retain trypsin inhibitory activity.


id: cord-023209-un2ysc2v
title: Poster Presentations
author: nan
date: 2008-10-07
txt: ./txt/cord-023209-un2ysc2v.txt
cache: ./cache/cord-023209-un2ysc2v.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167823/
doi: 10.1002/psc.1090
abstract: nan
summary:
  Site-specifi c PEGylation of human IgG1-Fab using a rationally designed trypsin variant In the present contribution we report on a novel, highly selective biocatalytic method enabling C-terminal modifi cations of proteins with artifi cial functionalities under native state conditions. Recently, our group report a novel approach to a totally synthetic vaccine which consists of FMDV (Foot and Mouth Disease Virus) VP1 peptides, prepared by covalent conjugation of peptide biomolecules with membrane active carbochain polyelectrolytes In the present study, peptide epitops of VP1 protein both 135-161(P1) amino acid residues (Ser-Lys-Tyr-Ser-Thr-Thr-Gly-Glu-Arg-Thr-Arg-Thr-Arg-Gly-Asp-Leu-Gly-Ala-Leu-Ala-Ala-Arg-Val-Ala-Thr-Gln-Leu-Pro-Ala) and triptophan (Trp) containing on the N terminus 135-161 amino acid residues (Trp-135-161) (P2) were synthesized by using the microwave assisted solid-phase methods. Using as a template a peptide, already identifi ed, with agonist activity against PTPRJ(H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), here we report a structure-activity study carried out through endocyclic modifi cations (Ala-scan, D-substitutions, single residue deletions, substitutions of the disulfi de bridge) and the preliminary biological results of this set of compounds.


id: cord-023225-5quigar4
title: Posters
author: nan
date: 2012-08-21
txt: ./txt/cord-023225-5quigar4.txt
cache: ./cache/cord-023225-5quigar4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167970/
doi: 10.1002/psc.2449
abstract: No abstract is available for this article.
summary:
  To further explore the structure-function relationship, a viable synthesis strategy for pseudodesmin A analogues was developed, based on side-chain attachment of the first amino acid to the solid support, followed by stepwise Fmoc solid-phase synthesis of the linear peptide precursor and on-resin head-to-tail cyclization. The cases when the amino acid sequence of a fragment coincided with part of the primary structure of a natural oligopeptide were recorded in the Total protein chemical synthesis requires a case by case design and optimization which is governed by factors such as the solubility of the individual peptide segments, their primary sequence and in particular the presence of "difficult" amino acid residues at ligation junctions such as proline or the location of cysteines. In this study we present synthesis of two series of peptide libraries, which were designed by substitution of Leu in the P5, P6 position of our control peptide (Ac-LLLLRVKR-AMBA) with each of nineteen amino acid residues in order to verifying its influence on activity and selectivity of the resulting analogues.


id: cord-023284-i0ecxgus
title: Abstracts of publications related to QASR
author: nan
date: 2006-09-19
txt: ./txt/cord-023284-i0ecxgus.txt
cache: ./cache/cord-023284-i0ecxgus.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168536/
doi: 10.1002/qsar.19900090309
abstract: nan
summary:
  Results: Methods developed for the investigation for the relationships between structure and toxic effects of compounds are summarized: a) The extra-thermodynamic approach: the Hansch paradigm, physical chemical properties that influence biological activity and their parametrization, originality of the Hansch approach, receptors and pharmacophores: the natural content of the Hansch approach, predictive value of QSARs, a statistifa1 tool: multiple linear regression analysis, the problem of correlations among molecular descriptors, other mathematical utilizations of extrathermodynamic parameters; b) The substructural approach: when topological (substructural) descriptors are needed, how to use topological decriptors; c) QSAR in mutagenicity and carcinogenicity: general problems, specific versions of the substructural approach used for mutagenicity and carcinogenicity, applications to mutagenicity and carcinogenicity.


id: cord-023442-4vzwc2d2
title: Proceedings of SCANNING 94/SEEMS 94 Charleston, South Carolina, USA
author: nan
date: 2006-12-05
txt: ./txt/cord-023442-4vzwc2d2.txt
cache: ./cache/cord-023442-4vzwc2d2.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169609/
doi: 10.1002/sca.4950160315
abstract: nan
summary:
  IV-4 Scanning Vol. 16, Supplement IV (1994) Simulation of image formation and detection systems in the SEM is a vital link in performing image analysis to obtain precise measurements, to provide the necessary connection between image parameters and structural dimensions, and to reflect important microscope beam and detector parameters. By knowing the transfer function, noise, and distortion figure in digital form, it is relatively easy to obtain more accurate comparison of the measured and calculated signal (Fig. 1 The calculation of image contrast in the scanning electron microscope (SEM) can be done using Monte Carlo techniques if the electron trajectories can be calculated through the composition profiles in the specimen. Specimens providing IV-18 Scanning Vol. 16, Supplement IV (1994) FIG highly redundant structures and relatively smooth fractures, such as cell suspensions or o/w emulsions, were investigated using freeze fracture/replication and ambient temperature transmission electron microscopy (AT-TEM).


id: cord-023726-2fduzqyb
title: The Structure of Viruses
author: STRAUSS, JAMES H.
date: 2012-07-27
txt: ./txt/cord-023726-2fduzqyb.txt
cache: ./cache/cord-023726-2fduzqyb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173534/
doi: 10.1016/b978-0-12-373741-0.50005-2
abstract: nan
summary:
  Also shown for each family is the presence or absence of an envelope in the virion, the triangulation number (defined later) if the virus is icosahedral, the morphology of the nucleocapsid or core, and figure numbers where the structures of members of a family are illustrated. Structural studies of viruses have shown that the capsid proteins that form the virions of many plant and animal icosahedral viruses have a common fold. The largest particle is the nucleocapsid of herpes simplex virus, which is 1250 Å in diameter and has T=16 symmetry (the virion is enveloped but only the nucleocapsid is regular FIGURE 2.5 Gallery of three-dimensional reconstructions of icosahedral viruses from cryoelectron micrographs. For most RNA viruses, nucleocapsids can be recognized as distinct structures within the infected cell and can be isolated from virions by treatment with detergents that dissolve the envelope.


id: cord-031957-df4luh5v
author: dos Santos-Silva, Carlos André
date: 2020-09-02
txt: ./txt/cord-031957-df4luh5v.txt
cache: ./cache/cord-031957-df4luh5v.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476358/
doi: 10.1177/1177932220952739
summary:
  19 Plant AMPs are the central focus of the present review, comprising information on their structural features (at genomic, gene, and protein levels), resources, and bioinformatic tools available, besides the proposition of an annotation routine. 26 Plant AMPs are also classified into families considering protein sequence similarity, cysteine motifs, and distinctive patterns of disulfide bonds, which determine the folding of the tertiary structure. 27, 31 These AMP categories will be detailed in the next sections, together with other groups here considered (Impatienlike, Macadamia [β-barrelins], Puroindoline (PIN), and Thaumatin-like protein [TLP]) and the recently described αhairpinin AMPs. The description includes comments on their structure, pattern for regular expression (REGEX) analysis (when available), functions, tissue-specificity, and scientific data availability. 179 As to the TLP structure, this protein presents characteristic thaumatin signature (PS00316): 180, 181 Most of the TLPs have molecular mass ranging from 21 to 26 kDa, 163 possessing 16 conserved cysteine residues (Supplementary Figure S8) involved in the formation of 8 disulfide bonds, 182 which help in the stability of the molecule, allowing a correct folding even under extreme conditions of temperature and pH.

title:
  Plant Antimicrobial Peptides: State of the Art, In Silico Prediction and Perspectives in the Omics Era

abstract:
  Even before the perception or interaction with pathogens, plants rely on constitutively guardian molecules, often specific to tissue or stage, with further expression after contact with the pathogen. These guardians include small molecules as antimicrobial peptides (AMPs), generally cysteine-rich, functioning to prevent pathogen establishment. Some of these AMPs are shared among eukaryotes (eg, defensins and cyclotides), others are plant specific (eg, snakins), while some are specific to certain plant families (such as heveins). When compared with other organisms, plants tend to present a higher amount of AMP isoforms due to gene duplications or polyploidy, an occurrence possibly also associated with the sessile habit of plants, which prevents them from evading biotic and environmental stresses. Therefore, plants arise as a rich resource for new AMPs. As these molecules are difficult to retrieve from databases using simple sequence alignments, a description of their characteristics and in silico (bioinformatics) approaches used to retrieve them is provided, considering resources and databases available. The possibilities and applications based on tools versus database approaches are considerable and have been so far underestimated.


id: cord-033010-o5kiadfm
author: Durojaye, Olanrewaju Ayodeji
date: 2020-10-02
txt: ./txt/cord-033010-o5kiadfm.txt
cache: ./cache/cord-033010-o5kiadfm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529470/
doi: 10.1186/s43042-020-00081-5
summary:
  RESULTS: This study describes the detailed computational process by which the 2019-nCoV main proteinase coding sequence was mapped out from the viral full genome, translated and the resultant amino acid sequence used in modeling the protein 3D structure. Our current study took advantage of the availability of the SARS CoV main proteinase amino acid sequence to map out the nucleotide coding region for the same protein in the 2019-nCoV. The predicted secondary structure composition shows a high degree of alpha helix and beta sheets, respectively, occupying 45 and 47% of the total residues with the percentage loop occupancy at 8% regarded as comparative modeling, constructs atomic models based on known structures or structures that have been determined experimentally and likewise share more than 40% sequence homology.

title:
  Potential therapeutic target identification in the novel 2019 coronavirus: insight from homology modeling and blind docking study

abstract:
  BACKGROUND: The 2019-nCoV which is regarded as a novel coronavirus is a positive-sense single-stranded RNA virus. It is infectious to humans and is the cause of the ongoing coronavirus outbreak which has elicited an emergency in public health and a call for immediate international concern has been linked to it. The coronavirus main proteinase which is also known as the 3C-like protease (3CLpro) is a very important protein in all coronaviruses for the role it plays in the replication of the virus and the proteolytic processing of the viral polyproteins. The resultant cytotoxic effect which is a product of consistent viral replication and proteolytic processing of polyproteins can be greatly reduced through the inhibition of the viral main proteinase activities. This makes the 3C-like protease of the coronavirus a potential and promising target for therapeutic agents against the viral infection. RESULTS: This study describes the detailed computational process by which the 2019-nCoV main proteinase coding sequence was mapped out from the viral full genome, translated and the resultant amino acid sequence used in modeling the protein 3D structure. Comparative physiochemical studies were carried out on the resultant target protein and its template while selected HIV protease inhibitors were docked against the protein binding sites which contained no co-crystallized ligand. CONCLUSION: In line with results from this study which has shown great consistency with other scientific findings on coronaviruses, we recommend the administration of the selected HIV protease inhibitors as first-line therapeutic agents for the treatment of the current coronavirus epidemic.


id: cord-102463-d440jsek
title: IG-VAE: Generative Modeling of Immunoglobulin Proteins by Direct 3D Coordinate Generation
author: Eguchi, Raphael R.
date: 2020-08-10
url: https://doi.org/10.1101/2020.08.07.242347
doi: 10.1101/2020.08.07.242347
abstract:
  While deep learning models have seen increasing applications in protein science, few have been implemented for protein backbone generation—an important task in structure-based problems such as active site and interface design. We present a new approach to building class-specific backbones, using a variational auto-encoder to directly generate the 3D coordinates of immunoglobulins. Our model is torsion- and distance-aware, learns a high-resolution embedding of the dataset, and generates novel, high-quality structures compatible with existing design tools. We show that the Ig-VAE can be used to create a computational model of a SARS-CoV2-RBD binder via latent space sampling. We further demonstrate that the model’s generative prior is a powerful tool for guiding computational protein design, motivating a new paradigm under which backbone design is solved as constrained optimization problem in the latent space of a generative model.


id: cord-103823-3rchp9yy
author: Taufer, Michela
date: 2008-11-30
url: https://api.elsevier.com/content/article/pii/S0167819108000902
doi: 10.1016/j.parco.2008.08.002
title:
  RNAVLab: A virtual laboratory for studying RNA secondary structures based on grid computing technology

abstract:
  Abstract As ribonucleic acid (RNA) molecules play important roles in many biological processes including gene expression and regulation, their secondary structures have been the focus of many recent studies. Despite the computing power of supercomputers, computationally predicting secondary structures with thermodynamic methods is still not feasible when the RNA molecules have long nucleotide sequences and include complex motifs such as pseudoknots. This paper presents RNAVLab (RNA Virtual Laboratory), a virtual laboratory for studying RNA secondary structures including pseudoknots that allows scientists to address this challenge. Two important case studies show the versatility and functionalities of RNAVLab. The first study quantifies its capability to rebuild longer secondary structures from motifs found in systematically sampled nucleotide segments. The extensive sampling and predictions are made feasible in a short turnaround time because of the grid technology used. The second study shows how RNAVLab allows scientists to study the viral RNA genome replication mechanisms used by members of the virus family Nodaviridae.


id: cord-171099-d0qr84xg
author: Buehler, Markus J.
date: 2020-03-30
txt: ./txt/cord-171099-d0qr84xg.txt
cache: ./cache/cord-171099-d0qr84xg.txt
extension: .txt
mime: text/plain
url: https://arxiv.org/pdf/2003.14258v1.pdf
doi: nan
summary:
  Presenting musical encoding in two versions one in the amino-acid scale and one based on equal temperament tuning the method allows for expressing protein structures in audible space, offering novel avenues to represent, analyze and design architectural features across lengthand time-scales. We further report a hierarchical frequency spectrum analysis of five distinct protein structures, which offer insights into how genetic mutations, and the binding of the virus spike protein to the human ACE2 cell receptor directly influence the audio. What you hear is a multi-layered algorithmic composition featuring both the vibrational spectrum of the entire protein (expressed in sound and rhythmic elements), the sequence and folding of amino acids that compose the virus spike structure, as well as interwoven melodiesforming counterpoint music -reflecting the complex hierarchical intersecting geometry of the protein.

title:
  Nanomechanical sonification of the 2019-nCoV coronavirus spike protein through a materiomusical approach

abstract:
  Proteins are key building blocks of virtually all life, providing the material foundation of spider silk, cells, and hair, but also offering other functions from enzymes to drugs, and pathogens like viruses. Based on a nanomechanical analysis of the structure and motions of atoms and molecules at multiple scales, we report sonified versions of the coronavirus spike protein of the pathogen of COVID-19, 2019-nCoV. The audio signal, created using a novel nanomechanical sonification method, features an overlay of the vibrational signatures of the protein's primary, secondary and higher-order structures. Presenting musical encoding in two versions - one in the amino-acid scale and one based on equal temperament tuning - the method allows for expressing protein structures in audible space, offering novel avenues to represent, analyze and design architectural features across length- and time-scales. We further report a hierarchical frequency spectrum analysis of five distinct protein structures, which offer insights into how genetic mutations, and the binding of the virus spike protein to the human ACE2 cell receptor directly influence the audio. Applications of the approach may include the development of de novo antibodies by designing protein sequences that match, through melodic counterpoints, the binding sites in the spike protein. Other applications of audible coding of matter include material design by manipulating sound, detecting mutations, and offering a way to reach out to broader communities to explain the physics of proteins. It also forms a physics-based compositional technique to create new art, referred to as materiomusic, which is akin to finding a new palette of colors for a painter. Here, the nanomechanical structure of matter, reflected in an oscillatory framework, presents a new palette for sound generation, and can complement or support human creativity.


id: cord-251982-vbchjexm
author: Sarikavak-Lisesivdin, B.
date: 2020-09-17
url: https://doi.org/10.1016/j.cplett.2020.138006
doi: 10.1016/j.cplett.2020.138006
title:
  Structural parameters and electronic properties of 2D carbon allotrope: graphene with a kagome lattice structure

abstract:
  In this paper, the electronic properties of a carbon allotrope, graphene with a kagome lattice structure, are investigated. Spin-polarized density functional theory (DFT) calculations with Grimme dispersion corrections were done. Bond lengths, electronic band structure, and projected density of states were calculated. Electronic band structure calculations show kagome flat-band formation with higher d-orbital contributed bonding behavior than the pristine graphene structure. The structural parameters and electronic band results of this 2D carbon allotrope show wider possible usage in many applications from desalination membranes to possible high-temperature superconductors.


id: cord-252166-qah877pk
title: In silico pharmacology for drug discovery: applications to targets and beyond
author: Ekins, S
date: 2007-09-01
txt: ./txt/cord-252166-qah877pk.txt
cache: ./cache/cord-252166-qah877pk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17549046/
doi: 10.1038/sj.bjp.0707306
summary:
  These in silico methods include databases, quantitative structure-activity relationships, similarity searching, pharmacophores, homology models and other molecular modeling, machine learning, data mining, network analysis tools and data analysis tools that use a computer. This included the development of methods and databases, quantitative structure-activity relationships (QSARs), similarity searching, pharmacophores, homology models and other molecular modelling, machine learning, data mining, network analysis and data analysis tools that all use a computer. For example, one study used probabilistic neural networks with 24 atom-type descriptors to classify 799 molecules from the MDL Drug Data Reports (MDDR) database with activity against one of the seven targets (G protein-coupled receptors (GPCRs), kinases, enzymes, nuclear hormone receptors and zinc peptidases) with excellent training, testing and prediction statistics (Niwa, 2004) . In silico pharmacology for drug discovery S Ekins et al derived with 40 molecules with activities over three log orders to result in a five-feature pharmacophore model.

abstract:
  Computational (in silico) methods have been developed and widely applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, similarity searching, pharmacophores, homology models and other molecular modeling, machine learning, data mining, network analysis tools and data analysis tools that use a computer. Such methods have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The first part of this review discussed the methods that have been used for virtual ligand and target-based screening and profiling to predict biological activity. The aim of this second part of the review is to illustrate some of the varied applications of in silico methods for pharmacology in terms of the targets addressed. We will also discuss some of the advantages and disadvantages of in silico methods with respect to in vitro and in vivo methods for pharmacology research. Our conclusion is that the in silico pharmacology paradigm is ongoing and presents a rich array of opportunities that will assist in expediating the discovery of new targets, and ultimately lead to compounds with predicted biological activity for these novel targets.


id: cord-254107-02bik024
title: Utility of homology models in the drug discovery process
author: Hillisch, Alexander
date: 2004-08-31
url: https://api.elsevier.com/content/article/pii/S1359644604031964
doi: 10.1016/s1359-6446(04)03196-4
abstract:
  Abstract Advances in bioinformatics and protein modeling algorithms, in addition to the enormous increase in experimental protein structure information, have aided in the generation of databases that comprise homology models of a significant portion of known genomic protein sequences. Currently, 3D structure information can be generated for up to 56% of all known proteins. However, there is considerable controversy concerning the real value of homology models for drug design. This review provides an overview of the latest developments in this area and includes selected examples of successful applications of the homology modeling technique to pharmaceutically relevant questions. In addition, the strengths and limitations of the application of homology models during all phases of the drug discovery process are discussed.


id: cord-257494-242k58ll
author: Bastos, Paulo
date: 2017-01-17
txt: ./txt/cord-257494-242k58ll.txt
cache: ./cache/cord-257494-242k58ll.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/med.21435
doi: 10.1002/med.21435
summary:
  1 Human host defense peptides are an intrinsic part of the innate immune system and exhibit a broad activity spectrum against bacteria, fungi, viruses, and parasites While AMPs can be antibacterial (ABPs), antifungal, antiprotist, antiviral, anticancer, antiparasitic, insecticidal, spermicidal, chemotactic, antioxidant, protease inhibitors, or even exhibit wound healing properties (Supporting Information Table S1), their scope of action overlaps considerably and some peptides show activity at several levels (Fig. 2 ). 75 Moreover, when stabilizing disulfide bridges between conserved cysteine residues in human AMPs with β-hairpin or β-sheet conformations are disrupted, the resulting linear peptides still maintain their antimicrobial properties despite losing membranolytic activity. 212, 213 However, it should be noted that the antimicrobial effects of encephalins and their derived peptides result mostly from animal studies and have not been adequately studied in human secretions, despite the high conservation of their sequences across species, which most likely contribute for the similar activity spectrum.

title:
  Human Antimicrobial Peptides in Bodily Fluids: Current Knowledge and Therapeutic Perspectives in the Postantibiotic Era

abstract:
  Antimicrobial peptides (AMPs) are an integral part of the innate immune defense mechanism of many organisms. Due to the alarming increase of resistance to antimicrobial therapeutics, a growing interest in alternative antimicrobial agents has led to the exploitation of AMPs, both synthetic and isolated from natural sources. Thus, many peptide‐based drugs have been the focus of increasing attention by many researchers not only in identifying novel AMPs, but in defining mechanisms of antimicrobial peptide activity as well. Herein, we review the available strategies for the identification of AMPs in human body fluids and their mechanism(s) of action. In addition, an overview of the distribution of AMPs across different human body fluids is provided, as well as its relation with microorganisms and infectious conditions.


id: cord-263017-rh86g4jk
title: Virus disinfection mechanisms: the role of virus composition, structure, and function
author: Wigginton, Krista Rule
date: 2011-12-09
txt: ./txt/cord-263017-rh86g4jk.txt
cache: ./cache/cord-263017-rh86g4jk.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.coviro.2011.11.003
doi: 10.1016/j.coviro.2011.11.003
summary:
  Non-culturable virus disinfection kinetics must be either determined with human charge studies or predicted using surrogate viruses that can be cultured in vitro but that differ in composition, structure, and function. Coupling structure and composition information aids in our understanding of virus reactivity X-ray crystal structures have been published for numerous enteric viruses [25,26 ,27] and with these reports have come a windfall of valuable information including the location and orientation of capsid protein residues. Specific questions include: 1) Which virus protein residues are involved with fundamental functions and how do these vary amongst different strains and species; 2) What specific chemical modifications take place in the genome and capsid during disinfection and what effects do these modifications have on virus structure and function; 3) How similar are disinfectant-induced modifications amongst various enteric viruses?

abstract:
  Drinking waters are treated for enteric virus via a number of disinfection techniques including chemical oxidants, irradiation, and heat, however the inactivation mechanisms during disinfection remain elusive. Owing to the fact that a number of significant waterborne virus strains are not readily culturable in vitro at this time (e.g. norovirus, hepatitis A), the susceptibility of these viruses to disinfection is largely unknown. An in-depth understanding of the mechanisms involved in virus inactivation would aid in predicting the susceptibility of non-culturable virus strains to disinfection and would foster the development of improved disinfection methods. Recent technological advances in virology research have provided a wealth of information on enteric virus compositions, structures, and biological functions. This knowledge will allow for physical/chemical descriptions of virus inactivation and thus further our understanding of virus disinfection to the most basic mechanistic level.


id: cord-264489-h1n9ywbd
title: Insight into the Structures of Interleukin-18 Systems
author: Roy, Urmi
date: 2020-07-31
txt: ./txt/cord-264489-h1n9ywbd.txt
cache: ./cache/cord-264489-h1n9ywbd.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1476927120302486
doi: 10.1016/j.compbiolchem.2020.107353
summary:
  The present study, including structural and molecular dynamics simulations, takes a close look at the structural stabilities of IL-18 and IL-18 receptor-bound ligand structures as functions of time. The results help to identify the conformational changes of the ligand due to receptor binding, as well as the structural orders of the apo and holo IL-18 protein complexes. This investigative approach assists in the proper identifications of therapeutic-targets, their structural-assemblies and consistent ligand-receptor interfacial interactions, and thus, plays a vital role in the development of new, innovative medicines (Freudenberg et al. The present simulation study examines the structural stabilities of the ligand-protein, IL-18 and IL-18 receptor (IL-18R) bound ligand structures as functions of time. We analyze here the conformational changes within the ligand-protein, due to receptor binding and, we also identify the possible structurally ordered and disordered region within the apo and holo (ligand-bound) protein complexes.

abstract:
  Structure-based molecular designs play a critical role in the context of next generation drug development. Besides their fundamental scientific aspects, the findings established in this approach have significant implications in the expansions of target-based therapies and vaccines. Interleukin-18 (IL-18), also known as interferon gamma (IFN-γ) inducing factor, is a pro-inflammatory cytokine. The IL-18 binds first to the IL-18α receptor and forms a lower affinity complex. Upon binding with IL-18β a hetero-trimeric complex with higher affinity is formed that initiates the signal transduction process. The present study, including structural and molecular dynamics simulations, takes a close look at the structural stabilities of IL-18 and IL-18 receptor-bound ligand structures as functions of time. The results help to identify the conformational changes of the ligand due to receptor binding, as well as the structural orders of the apo and holo IL-18 protein complexes.


id: cord-266543-ng9zr299
title: Virtual ligand screening: strategies, perspectives and limitations
author: Klebe, Gerhard
date: 2006-06-20
url: https://www.sciencedirect.com/science/article/pii/S1359644606001784
doi: 10.1016/j.drudis.2006.05.012
abstract:
  In contrast to high-throughput screening, in virtual ligand screening (VS), compounds are selected using computer programs to predict their binding to a target receptor. A key prerequisite is knowledge about the spatial and energetic criteria responsible for protein–ligand binding. The concepts and prerequisites to perform VS are summarized here, and explanations are sought for the enduring limitations of the technology. Target selection, analysis and preparation are discussed, as well as considerations about the compilation of candidate ligand libraries. The tools and strategies of a VS campaign, and the accuracy of scoring and ranking of the results, are also considered.


id: cord-266921-x9q7dwc4
title: Information available at cut rates: structure and mechanism of ribonucleases
author: Worrall, Jonathan AR
date: 2006-12-26
txt: ./txt/cord-266921-x9q7dwc4.txt
cache: ./cache/cord-266921-x9q7dwc4.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0959440X06002119
doi: 10.1016/j.sbi.2006.12.001
summary:
  The exoribonuclease RNase II is representative of an extensive enzyme family found in all three domains of life, whose members play roles in the maturation, turn-Structure and mechanism of ribonucleases Worrall and Luisi 131 Whereas DEAD-box helicases use the free energy of ATP binding and hydrolysis to disrupt secondary structure, RNase R transduces the favourable free energy of RNA backbone hydrolysis into mechanical work that translates the single-stranded substrate further into the catalytic pocket, much like a ratchet. Crystal structures of the core of the exosomes from the archaea Sulfolobus solfataricus and Archaeoglobus fulgidus have recently become available, revealing a hexameric ring comprising two types of RNase-PH-like subunits, known as Rrp41 and Rrp42 (rRNA-processing proteins 41 and 42; see Figure 4a ) [36 ,37 ,38 ] . Structure of Escherichia coli RNase E catalytic domain and its implications for RNA turnover and processing

abstract:
  Ribonucleases are counterweights in the balance of gene expression and are also involved in the maturation of functional RNA. Recent structural data reveal how ribonucleases recognize and cleave targets, in most cases with the catalytic assistance of metal cofactors. Many of these enzymes are ‘processive’, in that they make multiple scissions following the binding of substrates; crystallographic data can account for this solution behaviour. These data not only explain how ribonucleases turn over transcripts, but also provide hints about how they often play dual roles in quality control checks on structured RNA.


id: cord-270587-k56fze59
title: Three-Dimensional Structures of Carbohydrates and Where to Find Them
author: Scherbinina, Sofya I.
date: 2020-10-18
txt: ./txt/cord-270587-k56fze59.txt
cache: ./cache/cord-270587-k56fze59.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/ijms21207702
doi: 10.3390/ijms21207702
summary:
  • Database can be freely accessed through web user interface; • Database must contain experimentally confirmed and/or predicted 3D structures (preprocessed and/or generated on-the-fly from a primary structure input) of glycans, glycoproteins, or protein-carbohydrate complexes; • Stored 3D structures must be deposited as atomic coordinates in PDB, MOL, or other format, and the structures must contain a saccharide moiety; • • Database can be freely accessed through web user interface; • Database must contain experimentally confirmed and/or predicted 3D structures (preprocessed and/or generated on-the-fly from a primary structure input) of glycans, glycoproteins, or protein-carbohydrate complexes; • Stored 3D structures must be deposited as atomic coordinates in PDB, MOL, or other format, and the structures must contain a saccharide moiety; • Currently, CHARMM36 parameterization features include monosaccharides in furanose [171] and pyranose [172] forms, glycosidic linkages between monosaccharides [171, 173] , complex carbohydrates and glycoproteins Detailed comparisons of all-chemical and dedicated force fields in a context of glycan modeling have been published [114, 139, 151, 167] .

abstract:
  Analysis and systematization of accumulated data on carbohydrate structural diversity is a subject of great interest for structural glycobiology. Despite being a challenging task, development of computational methods for efficient treatment and management of spatial (3D) structural features of carbohydrates breaks new ground in modern glycoscience. This review is dedicated to approaches of chemo- and glyco-informatics towards 3D structural data generation, deposition and processing in regard to carbohydrates and their derivatives. Databases, molecular modeling and experimental data validation services, and structure visualization facilities developed for last five years are reviewed.


id: cord-278135-kvuti410
title: Developments, applications, and prospects of cryo‐electron microscopy
author: Benjin, Xu
date: 2019-12-26
txt: ./txt/cord-278135-kvuti410.txt
cache: ./cache/cord-278135-kvuti410.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/pro.3805
doi: 10.1002/pro.3805
summary:
  Blue corresponds to structures determined by X-ray crystallography, dark orange corresponds to structures determined by nuclear magnetic resonance, and gray corresponds to structures determined by electron microscopy and NMR, cryo-EM has the following advantages: (a) it does not need crystals; (b) it is suitable for proteins and their complexes of large molecular weight; (c) it reduces radiation damage and maintains the native activity and functional state of samples, including posttranslational modifications; (d) multiple different conformational states can be captured in one experiment; (e) it is suitable for the structural analysis of membrane proteins such as GPCR and their complexes; (f) when encountering some structures that cannot be resolved by conventional X-ray crystallography, cryo-EM is still the mainstream.

abstract:
  Cryo‐electron microscopy (cryo‐EM) is a structural biological method that is used to determine the 3D structures of biomacromolecules. After years of development, cryo‐EM has made great achievements, which has led to a revolution in structural biology. In this article, the principle, characteristics, history, current situation, workflow, and common problems of cryo‐EM are systematically reviewed. In addition, the new development direction of cryo‐EM—cryo‐electron tomography (cryo‐ET), is discussed in detail. Also, cryo‐EM is prospected from the following aspects: the structural analysis of small proteins, the improvement of resolution and efficiency, and the relationship between cryo‐EM and drug development. This review is dedicated to giving readers a comprehensive understanding of the development and application of cryo‐EM, and to bringing them new insights.


id: cord-282035-jibmg4ch
author: Dunbar, R. I. M.
date: 2020-08-26
url: https://doi.org/10.1098/rspa.2020.0446
doi: 10.1098/rspa.2020.0446
title:
  Structure and function in human and primate social networks: implications for diffusion, network stability and health

abstract:
  The human social world is orders of magnitude smaller than our highly urbanized world might lead us to suppose. In addition, human social networks have a very distinct fractal structure similar to that observed in other primates. In part, this reflects a cognitive constraint, and in part a time constraint, on the capacity for interaction. Structured networks of this kind have a significant effect on the rates of transmission of both disease and information. Because the cognitive mechanism underpinning network structure is based on trust, internal and external threats that undermine trust or constrain interaction inevitably result in the fragmentation and restructuring of networks. In contexts where network sizes are smaller, this is likely to have significant impacts on psychological and physical health risks.


id: cord-283491-y6t64pux
title: Covid‐19.bioreproducibility.org: A web resource for SARS‐CoV‐2‐related structural models
author: Brzezinski, Dariusz
date: 2020-09-27
txt: ./txt/cord-283491-y6t64pux.txt
cache: ./cache/cord-283491-y6t64pux.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32981130/
doi: 10.1002/pro.3959
summary:
  Understandably, firstline research findings, including molecular structure determinations, depositions in the Protein Data Bank (PDB), 1 and related results, are often made public on BioRxiv 2 or MedRxiv 3 before formal peer review. In this paper, we present covid-19.bioreproduciblity.org, a web resource that organizes SARS-CoV-2 related structural information in a way that should be understandable and useful for a wider scientific community, and not only for structural biologists. Finally, the structures are evaluated by a team of expert structural biologists who use a combination of the mined data, validation reports, and manual inspection of the protein models and associated electron density to examine potential problems. If raw diffraction data are available, the results of automatic processing of images by HKL-3000auto are examined to verify that the structure was determined in the correct space group and at optimal resolution.

abstract:
  The COVID‐19 pandemic has triggered numerous scientific activities aimed at understanding the SARS‐CoV‐2 virus and ultimately developing treatments. Structural biologists have already determined hundreds of experimental X‐ray, cryo‐EM, and NMR structures of proteins and nucleic acids related to this coronavirus, and this number is still growing. To help biomedical researchers, who may not necessarily be experts in structural biology, navigate through the flood of structural models, we have created an online resource, covid19.bioreproducibility.org, that aggregates expert‐verified information about SARS‐CoV‐2‐related macromolecular models. In this paper, we describe this web resource along with the suite of tools and methodologies used for assessing the structures presented therein. This article is protected by copyright. All rights reserved.


id: cord-287450-hydy874v
title: Structures and diseases
author: Wendt, K Ulrich
date: 2008
txt: ./txt/cord-287450-hydy874v.txt
cache: ./cache/cord-287450-hydy874v.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/18250627/
doi: 10.1038/nsmb0208-117
summary:
  In early September 2007, about 180 structural biologists and biochemists met in the picturesque town of Murnau, located near Staffelsee Lake in the Bavarian alpine upland, to reflect on these questions and discuss recent biostructural data on the molecular determinants of human diseases, including microbial and viral infections, protein misfolding diseases, cancer and metabolic disorders. Starting the session on viral diseases, Rolf Hilgenfeld (University of Lübeck) reviewed the work from his laboratory on proteases of RNA viruses, such as severe acute respiratory syndrome (SARS) coronavirus and coxsackievirus B3, and also highlighted recent structural data on falcipain-2 from Plasmodium falciparum, discussing implications for the design of active-site directed and allosteric inhibitors for these cysteine proteases 14 . Günter Fritz (University of Konstanz) presented the unpublished structure of the ligand binding domain of RAGE, a multiligand receptor for advanced glycation end products, S100 proteins, HMGB1 and amyloid-β, whose activation is key to numerous chronic diseases such as diabetes, inflammation, arteriosclerosis and neurodegeneration, making it a potential therapeutic target 32, 33 .

abstract:
  Structural biology is making significant contributions toward an understanding of molecular constituents and mechanisms underlying human diseases at an atomic resolution, as discussed at the international Murnau Conference on Structural Biology of Disease Mechanisms held in September 2007 in Murnau, Germany.


id: cord-292483-u0ycqelc
title: Future prospects
author: Rossmann, Michael G.
date: 2011-04-16
url: https://doi.org/10.1016/b978-0-12-386507-6.00005-1
doi: 10.1016/b978-0-12-386507-6.00005-1
abstract:
  Cryo-electron microscopy (cryo-EM) in combination with single-particle analysis has begun to complement crystallography in the study of large macromolecules at near-atomic resolution. Furthermore, advances in cryo-electron tomography have made possible the study of macromolecules within their cellular environment. Single-particle and tomographic studies will become even more useful when technologies for improving the signal-to-noise ratio such as direct electron detectors and phase plates become widely available. Automated image acquisition has significantly reduced the time and effort required to determine the structures of macromolecular assemblies. As a result, the number of structures determined by cryo-EM is growing exponentially. However, there is an urgent need for improved criteria for validating both the reconstruction process and the atomic models derived from cryo-EM data. Another major challenge will be mitigating the effects of anisotropy caused by the missing wedge and the excessively low signal-to-noise ratio for tomographic data. Parallels between the development of macromolecular crystallography and cryo-EM have been used to tentatively predict the future of cryo-EM.


id: cord-292985-w62xaa4f
title: Flexibility and mobility of SARS-CoV-2-related protein structures
author: Römer, Rudolf A.
date: 2020-07-12
txt: ./txt/cord-292985-w62xaa4f.txt
cache: ./cache/cord-292985-w62xaa4f.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.07.12.199364
doi: 10.1101/2020.07.12.199364
summary:
  We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. 34 We have performed our analysis through multiple conformational steps starting from the crystal structures of SARS-CoV-2-related proteins as currently deposited in the PDB. In Fig. 1 (a) we see that for the crystal structure of SARS-CoV-2 nucleocapsid protein N-terminal RNA binding domain (PDB:6m3m), the largest rigid cluster in the pristine structure, i.e. at E cut = 0, largely remains rigid through the dilution process of consecutively lowering E cut values. Last, a protein with 2nd-order rigidity should have the most complex behaviour in terms of flexibility since new possible mobility can be expected throughout the range of E cut values. Moving along directions proposed by an elastic normal model analysis of the crystal structure, we can therefore construct possible motion trajectories that are fully consistent with the bond network and steric constraints.

abstract:
  The worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of SARS-CoV-2 drug targets, i.e. SARS-CoV-2 protein structures as deposited on the Protein Databank (PDB). We study their flexibility, rigidity and mobility, an important first step in trying to ascertain their dynamics for further drug-related docking studies. We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. For example, for the SARS-CoV-2 spike protein in the open configuration, our method identifies a possible further opening and closing of the S1 subunit through movement of SB domain. With full structural information of this process available, docking studies with possible drug structures are then possible in silico. In our study, we present full results for the more than 200 thus far published SARS-CoV-2-related protein structures in the PDB.


id: cord-301827-a7hnuxy5
title: A decade and a half of protein intrinsic disorder: Biology still waits for physics
author: Uversky, Vladimir N
date: 2013-04-29
txt: ./txt/cord-301827-a7hnuxy5.txt
cache: ./cache/cord-301827-a7hnuxy5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/pro.2261
doi: 10.1002/pro.2261
summary:
  94 Therefore, the abundance and peculiarities of the charged residues distribution within the protein sequences might determine physical and biological properties of extended IDPs and IDPRs. Also, simple polymer physics-based reasoning can give reasonably well-justified explanation of the conformational behavior of extended IDPs. In general, the conformational behavior of IDPs is characterized by the low cooperativity (or the complete lack thereof) of the denaturant-induced unfolding, lack of the measurable excess heat absorption peak(s) characteristic for the melting of ordered proteins, "turned out" response to heat and changes in pH, and the ability to gain structure in the presence of various binding partners. 183 This analysis revealed that proteins involved in regulation and execution of PCD possess substantial amount of intrinsic disorder and IDPRs were implemented in a number of crucial functions, such as protein-protein interactions, interactions with other partners including nucleic acids and other ligands, were shown to be enriched in post-translational modification sites, and were characterized by specific evolutionary patterns.

abstract:
  The abundant existence of proteins and regions that possess specific functions without being uniquely folded into unique 3D structures has become accepted by a significant number of protein scientists. Sequences of these intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are characterized by a number of specific features, such as low overall hydrophobicity and high net charge which makes these proteins predictable. IDPs/IDPRs possess large hydrodynamic volumes, low contents of ordered secondary structure, and are characterized by high structural heterogeneity. They are very flexible, but some may undergo disorder to order transitions in the presence of natural ligands. The degree of these structural rearrangements varies over a very wide range. IDPs/IDPRs are tightly controlled under the normal conditions and have numerous specific functions that complement functions of ordered proteins and domains. When lacking proper control, they have multiple roles in pathogenesis of various human diseases. Gaining structural and functional information about these proteins is a challenge, since they do not typically “freeze” while their “pictures are taken.” However, despite or perhaps because of the experimental challenges, these fuzzy objects with fuzzy structures and fuzzy functions are among the most interesting targets for modern protein research. This review briefly summarizes some of the recent advances in this exciting field and considers some of the basic lessons learned from the analysis of physics, chemistry, and biology of IDPs.


id: cord-304794-z2kx314h
title: G-quadruplexes in viruses: function and potential therapeutic applications
author: Métifiot, Mathieu
date: 2014-11-10
txt: ./txt/cord-304794-z2kx314h.txt
cache: ./cache/cord-304794-z2kx314h.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/nar/gku999
doi: 10.1093/nar/gku999
summary:
  Conversely, a G-quadruplex or G4 is formed by nucleic acid sequences (DNA or RNA) containing G-tracts or Gblocks (adjacent runs of guanines) and composed of various numbers of guanines. Short RNA templates from the central region of the HIV-1 genome contain G-rich sequences near the central polypurine tract (cPPT) at the 3 end of the pol gene (IN coding sequence); this is a region where one of the two primers used for synthesizing the (−) strand DNA is produced during reverse transcription. In addition, one could imagine alternative therapeutic strategies focused on targeting RNA structures within viral ORFs to interfere with the virus cycle as well as to promote antigen presentation and to stimulate the host immune response. Topology of a DNA G-quadruplex structure formed in the HIV-1 promoter: a potential target for anti-HIV drug development U3 Region in the HIV-1 genome adopts a G-quadruplex structure in its RNA and DNA sequence

abstract:
  G-rich nucleic acids can form non-canonical G-quadruplex structures (G4s) in which four guanines fold in a planar arrangement through Hoogsteen hydrogen bonds. Although many biochemical and structural studies have focused on DNA sequences containing successive, adjacent guanines that spontaneously fold into G4s, evidence for their in vivo relevance has recently begun to accumulate. Complete sequencing of the human genome highlighted the presence of ∼300 000 sequences that can potentially form G4s. Likewise, the presence of putative G4-sequences has been reported in various viruses genomes [e.g., Human immunodeficiency virus (HIV-1), Epstein–Barr virus (EBV), papillomavirus (HPV)]. Many studies have focused on telomeric G4s and how their dynamics are regulated to enable telomere synthesis. Moreover, a role for G4s has been proposed in cellular and viral replication, recombination and gene expression control. In parallel, DNA aptamers that form G4s have been described as inhibitors and diagnostic tools to detect viruses [e.g., hepatitis A virus (HAV), EBV, cauliflower mosaic virus (CaMV), severe acute respiratory syndrome virus (SARS), simian virus 40 (SV40)]. Here, special emphasis will be given to the possible role of these structures in a virus life cycle as well as the use of G4-forming oligonucleotides as potential antiviral agents and innovative tools.


id: cord-310192-8x37nx4s
author: Zhang, Huaqun
date: 2019-04-25
url: https://doi.org/10.1002/wrna.1541
doi: 10.1002/wrna.1541
title:
  Advances that facilitate the study of large RNA structure and dynamics by nuclear magnetic resonance spectroscopy

abstract:
  The characterization of functional yet nonprotein coding (nc) RNAs has expanded the role of RNA in the cell from a passive player in the central dogma of molecular biology to an active regulator of gene expression. The misregulation of ncRNA function has been linked with a variety of diseases and disorders ranging from cancers to neurodegeneration. However, a detailed molecular understanding of how ncRNAs function has been limited; due, in part, to the difficulties associated with obtaining high‐resolution structures of large RNAs. Tertiary structure determination of RNA as a whole is hampered by various technical challenges, all of which are exacerbated as the size of the RNA increases. Namely, RNAs tend to be highly flexible and dynamic molecules, which are difficult to crystallize. Biomolecular nuclear magnetic resonance (NMR) spectroscopy offers a viable alternative to determining the structure of large RNA molecules that do not readily crystallize, but is itself hindered by some technical limitations. Recently, a series of advancements have allowed the biomolecular NMR field to overcome, at least in part, some of these limitations. These advances include improvements in sample preparation strategies as well as methodological improvements. Together, these innovations pave the way for the study of ever larger RNA molecules that have important biological function. RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry. Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs. RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems.


id: cord-310847-63gh2tg4
author: Uversky, Vladimir N
date: 2013-04-01
txt: ./txt/cord-310847-63gh2tg4.txt
cache: ./cache/cord-310847-63gh2tg4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.4161/idp.24684
doi: 10.4161/idp.24684
summary:
  5, 10, 46 In fact, in comparison with ordered proteins, IDPs/IDPRs are characterized by noticeable biases in their amino acid compositions, 5, 8, 10, [46] [47] [48] containing less of so-called "order-promoting" residues (cysteine, tryptophan, isoleucine, tyrosine, phenylalanine, leucine, histidine, valine, asparagines and methionine, which are mostly hydrophobic residues which are commonly found within the hydrophobic cores of foldable proteins) and more of "disorder-promoting" residues (lysine, glutamine, serine, glutamic acid and proline, which are mostly polar and charged residues, which are typically located at the surface of foldable proteins) (Fig. 1A) . Glutamic acid is an important functional residue of ordered proteins, where it can be involved in the formation of specific electrostatic valves inside the pores of ion channels, or can play unique catalytic roles in the active sites

title:
  The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins

abstract:
  The ability of a protein to fold into unique functional state or to stay intrinsically disordered is encoded in its amino acid sequence. Both ordered and intrinsically disordered proteins (IDPs) are natural polypeptides that use the same arsenal of 20 proteinogenic amino acid residues as their major building blocks. The exceptional structural plasticity of IDPs, their capability to exist as heterogeneous structural ensembles and their wide array of important disorder-based biological functions that complements functional repertoire of ordered proteins are all rooted within the peculiar differential usage of these building blocks by ordered proteins and IDPs. In fact, some residues (so-called disorder-promoting residues) are noticeably more common in IDPs than in sequences of ordered proteins, which, in their turn, are enriched in several order-promoting residues. Furthermore, residues can be arranged according to their “disorder promoting potencies,” which are evaluated based on the relative abundances of various amino acids in ordered and disordered proteins. This review continues a series of publications on the roles of different amino acids in defining the phenomenon of protein intrinsic disorder and concerns glutamic acid, which is the second most disorder-promoting residue.


id: cord-312946-p2iazl7z
author: Ziółkowska, Natasza E.
date: 2006-07-18
txt: ./txt/cord-312946-p2iazl7z.txt
cache: ./cache/cord-312946-p2iazl7z.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0969212606002565
doi: 10.1016/j.str.2006.05.017
summary:
  The crystal structure of griffithsin, an antiviral lectin from the red alga Griffithsia sp., was solved and refined at 1.3 Å resolution for the free protein and 0.94 Å for a complex with mannose. Antiviral potency of griffithsin is likely due to the presence of multiple, similar sugar binding sites that provide redundant attachment points for complex carbohydrate molecules present on viral envelopes. Another conserved broad loop with the GGSGG sequence, 86-90, is located near the secondary carbohydrate binding site in calsepa and follows a course quite different than in banana and parkia lectins, yet similar to the path in the other proteins. The second crystal form, grown from material expressed in plants and containing only 121 residues in a protein chain, was orthorhombic (P2 1 2 1 2 1 ) and contained two griffithsin molecules in the asymmetric unit.

title:
  Domain-Swapped Structure of the Potent Antiviral Protein Griffithsin and Its Mode of Carbohydrate Binding

abstract:
  The crystal structure of griffithsin, an antiviral lectin from the red alga Griffithsia sp., was solved and refined at 1.3 Å resolution for the free protein and 0.94 Å for a complex with mannose. Griffithsin molecules form a domain-swapped dimer, in which two β strands of one molecule complete a β prism consisting of three four-stranded sheets, with an approximate 3-fold axis, of another molecule. The structure of each monomer bears close resemblance to jacalin-related lectins, but its dimeric structure is unique. The structures of complexes of griffithsin with mannose and N-acetylglucosamine defined the locations of three almost identical carbohydrate binding sites on each monomer. We have also shown that griffithsin is a potent inhibitor of the coronavirus responsible for severe acute respiratory syndrome (SARS). Antiviral potency of griffithsin is likely due to the presence of multiple, similar sugar binding sites that provide redundant attachment points for complex carbohydrate molecules present on viral envelopes.


id: cord-313694-p2sgaypq
title: Current ideas on the significance of protein glycosylation
author: West, Christopher M.
date: 1986
txt: ./txt/cord-313694-p2sgaypq.txt
cache: ./cache/cord-313694-p2sgaypq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/3029560/
doi: 10.1007/bf00230632
summary:
  The alternate view is that carbohydrate structures participate in numerous specific interactions with discrete protein receptors, and that these interactions lead to predictable modifications in the localization or activity of the glycoprotein. The notion of a ''non-specific'' role for carbohydrate has received perhaps its strongest support from studies on cells whose glycosylation processes have been globally altered by mutation or drugs. Consideration of the possible role of carbohydrate in other molecular associations with the plasma membrane will be considered below in sections on hormone-receptor interactions and cellsubstratum (e.g., extracellular matrix) and cell-cell adhesion. Considerable evidence has been adduced that various parasites such as viruses, bacteria, protozoa, etc., possess carbohydrate binding proteins which can interact with sugar structures on the surfaces of cells with which the parasites associate (167, 168, (116) (117) (118) (119) . In any case, antibodies and lectins may model potential receptors in cells which might specifically recognize carbohydrate-associated structures.

abstract:
  Carbohydrate has been removed from a number of glycoproteins without major effect on the structure or enzyme activity of the protein. Thus carbohydrate has been suggested to underly a non-primary function for proteins, such as in relatively non-specific interactions with other carbohydrates or macromolecules, stabilization of protein conformation, or protection from proteolysis. This non-specific concept is consistent with both the general similarity in carbohydrate structure on very diverse glycoproteins and the frequent structural microheterogeneity of carbohydrate chains at given sites. The concept is supported in a general sense by the viability of cells whose glycosylation processes have been globally disrupted by mutation or pharmacological inhibitors. In contrast to the above observations, other studies have revealed the existence of specific, selective receptors for discrete oligosaccharide structures on glycoproteins which seem to be important for compartmentalization of the glycoprotein, or the positioning of cells on which the glycoprotein is concentrated. Sometimes multivalency in the carbohydrate-receptor interaction is crucial. There are additional possible roles for carbohydrate in the transduction of information upon binding to a receptor. The possibility of specific roles for carbohydrate is supported by the existence of numerous unique carbohydrate structures, many of which have been detected as glycoantigens by monoclonal antibodies, with unique distributions in developing and differentiated cells. This article attempts to summarize and rationalize the contradictory results. It appears that in general carbohydrate does in fact underlie only roles secondary to a protein's primary function. These secondary roles are simple non-specific ones of protection and stabilization, but often also satisfy the more sophisticated needs of spatial position control and compartmentalization in multicellular eukaryotic organisms. It is suggested that there are advantages, evolutionarily speaking, for the shared use of carbohydrate for non-specific roles and for specific roles primarily as luxury functions to be executed during the processes of cell differentiation and morphogenesis.


id: cord-314321-klb8oe9q
author: Chen, Serena H.
date: 2020-04-18
url: https://doi.org/10.1101/2020.04.17.047548
doi: 10.1101/2020.04.17.047548
title:
  Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets

abstract:
  The emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19.


id: cord-314329-rzda8x62
title: Rigidity, normal modes and flexible motion of a SARS-CoV-2 (COVID-19) protease structure
author: Wells, Stephen A.
date: 2020-03-12
url: https://doi.org/10.1101/2020.03.10.986190
doi: 10.1101/2020.03.10.986190
abstract:
  The rigidity and flexibility of two recently reported crystal structures (PDB entries 6Y2E and 6LU7) of a protease from the SARS-CoV-2 virus, the infectious agent of the COVID-19 respiratory disease, has been investigated using pebble-game rigidity analysis, elastic network model normal mode analysis, and all-atom geometric simulations. This computational investigation of the viral protease follows protocols that have been effective in studying other homodimeric enzymes. The protease is predicted to display flexible motions in vivo which directly affect the geometry of a known inhibitor binding site and which open new potential binding sites elsewhere in the structure. A database of generated PDB files representing natural flexible variations on the crystal structures has been produced and made available for download from an institutional data archive. This information may inform structure-based drug design and fragment screening efforts aimed at identifying specific antiviral therapies for the treatment of COVID-19.


id: cord-319906-s7kzp795
author: Zemla, Adam T
date: 2011-06-02
txt: ./txt/cord-319906-s7kzp795.txt
cache: ./cache/cord-319906-s7kzp795.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/21635786/
doi: 10.1186/1471-2105-12-226
summary:
  When for a given reference structure a structure-based search is performed on a set of proteins from the Protein Data Bank (PDB), StralSV identifies all structurally similar fragments from that set, evaluates the calculated structure-based alignments between the query (reference) motif (designated "segment" in this work) and the detected structure fragments, and quantifies the observed sequence variability at each residue position on the query structure. (For an illustration of a "span", see additional file 1: StralSV-RdRp_Suppl_Figure 1.docx.) All residue-residue pairs that are contained within a span''s alignment are used to calculate the sequence variability data at the corresponding position in the query structure. The qualified hits (structure fragments from PDB with detected local similarities to the query structure) for six selected sequence positions (positional hits) of polio RdRp (positions identified in Figure 3 ) were categorized and quantified based on SCOP (Structure Classification of Proteins database; version 1.75, June 2009 release) identifiers [32] .

title:
  StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase

abstract:
  BACKGROUND: Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. RESULTS: Here we present StralSV (structure-alignment sequence variability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. CONCLUSIONS: StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.


id: cord-322885-ob5euspo
author: Durdagi, Serdar
date: 2020-09-09
txt: ./txt/cord-322885-ob5euspo.txt
cache: ./cache/cord-322885-ob5euspo.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.09.09.287987
doi: 10.1101/2020.09.09.287987
summary:
  One Sentence Summary Radiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19. Radiation-damage-free SFX method which enables obtaining the novel high-resolution ambient-temperature structures of the binding pocket of Mpro provides an unprecedented opportunity for identification of highly effective inhibitors for drug repurposing by using a hybrid approach that combines structural and in silico methods. We determined two radiation-damage-free SFX crystal structures of SARS-CoV-2 Mpro in two crystal forms at 1.9 Å and 2.1 Å resolutions with the following PDB IDs: 7CWB and 7CWC, respectively (Fig. 1A, B) (Supplementary Table 1&2 The diffraction data collected remotely at the MFX instrument of the LCLS at SLAC National Laboratory, Menlo Park, CA (Sierra et al., They reveal novel active site residue conformations and dynamics at atomic level, revealing several differences compared to the prior ambient-temperature structure of SARS-CoV-2 Mpro that was obtained at a home X-ray source (Fig. 1A, B ).

title:
  Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing

abstract:
  The COVID19 pandemic has resulted in 25+ million reported infections and nearly 850.000 deaths. Research to identify effective therapies for COVID19 includes: i) designing a vaccine as future protection; ii) structure-based drug design; and iii) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determined two apo structures of Severe Acute Respiratory Syndrome CoronaVirus-2 main protease at ambienttemperature by Serial Femtosecond X-ray crystallography. We employed detailed molecular simulations of selected known main protease inhibitors with the structures and compared binding modes and energies. The combined structural biology and molecular modeling studies not only reveal the dynamics of small molecules targeting main protease but will also provide invaluable opportunities for drug repurposing and structure-based drug design studies against SARS-CoV-2. One Sentence Summary Radiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19.


id: cord-324410-be2ith3z
author: Wang, Qi
date: 2007-06-13
txt: ./txt/cord-324410-be2ith3z.txt
cache: ./cache/cord-324410-be2ith3z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17565384/
doi: 10.1371/journal.pone.0000531
summary:
  These results demonstrate the significant influence of crystal packing on small molecule complexation and suggest that EUDOC is able to predict small-molecule complexes and that it is useful for the design of new materials, molecular sensors, and multimeric inhibitors of protein-protein interactions. To expand the application of the EUDOC program to supramolecular chemistry, we tested its ability to reproduce the crystal structures of small-molecule guest-host complexes. Herein we report the results of our docking studies with 161 selected crystal structures of small-molecule guest-host complexes using the EUDOC program. These results show that the program is able to reproduce all 161 crystal structures and that the average interaction energy of these small-molecule complexes (250.1 kcal/mol) is nearly half of that of the 153 small molecule-bound protein complexes we studied in previous tests (2108.5 kcal/mol). The results also demonstrate the significant influence of crystal packing on small-molecule complex crystal structures and suggest that the EUDOC program is able to predict 3D structures of small-molecule guest-host complexes with reasonable reliability.

title:
  Accurate Reproduction of 161 Small-Molecule Complex Crystal Structures using the EUDOC Program: Expanding the Use of EUDOC to Supramolecular Chemistry

abstract:
  EUDOC is a docking program that has successfully predicted small-molecule-bound protein complexes and identified drug leads from chemical databases. To expand the application of the EUDOC program to supramolecular chemistry, we tested its ability to reproduce crystal structures of small-molecule complexes. Of 161 selected crystal structures of small-molecule guest-host complexes, EUDOC reproduced all these crystal structures with guest structure mass-weighted root mean square deviations (mwRMSDs) of <1.0 Å relative to the corresponding crystal structures. In addition, the average interaction energy of these 161 guest-host complexes (−50.1 kcal/mol) was found to be nearly half of that of 153 previously tested small-molecule-bound protein complexes (−108.5 kcal/mol), according to the interaction energies calculated by EUDOC. 31 of the 161 complexes could not be reproduced with mwRMSDs of <1.0 Å if neighboring hosts in the crystal structure of a guest-host complex were not included as part of the multimeric host system, whereas two of the 161 complexes could not be reproduced with mwRMSDs of <1.0 Å if water molecules were excluded from the host system. These results demonstrate the significant influence of crystal packing on small molecule complexation and suggest that EUDOC is able to predict small-molecule complexes and that it is useful for the design of new materials, molecular sensors, and multimeric inhibitors of protein-protein interactions.


id: cord-325328-3l3jznkj
title: RNA structure: the long and the short of it
author: Holbrook, Stephen R
date: 2005-05-16
txt: ./txt/cord-325328-3l3jznkj.txt
cache: ./cache/cord-325328-3l3jznkj.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0959440X05000849
doi: 10.1016/j.sbi.2005.04.005
summary:
  Structural studies and comparative sequence analyses have suggested that biological RNAs are largely modular in nature, composed primarily of conserved structural building blocks or motifs [4] of secondary (helices, and internal, external and junction loops) and tertiary (coaxial stacks, kissing hairpin loops, ribose zippers, etc.) structure. Other structures include the specificity domains of both A[17] and B-type ribonuclease P [18 ] ; RNAs corresponding to a guanine-responsive riboswitch (xpt) complexed with guanine [19 ] or hypoxanthine [20] , and an adenosine-responsive riboswitch (add) complexed with adenosine [19 ] ; a highly conserved stem-loop motif found at the 3 0 end of the genome of SARS (severe acute respiratory syndrome) virus and other coronaviruses [21 ] ; the core encapsidation signal of MMLV [2 ] ; and complexes between a high-affinity RNA aptamer and the NF-kB p50 homodimer [22] , and between the archaeal RNAbinding protein L7Ae and an RNA K-turn derived from a H/ACA small RNA [23] .

abstract:
  The database of RNA structure has grown tremendously since the crystal structure analyses of ribosomal subunits in 2000–2001. During the past year, the trend toward determining the structure of large, complex biological RNAs has accelerated, with the analysis of three intact group I introns, A- and B-type ribonuclease P RNAs, a riboswitch–substrate complex and other structures. The growing database of RNA structures, coupled with efforts directed at the standardization of nomenclature and classification of motifs, has resulted in the identification and characterization of numerous RNA secondary and tertiary structure motifs. Because a large proportion of RNA structure can now be shown to be composed of these recurring structural motifs, a view of RNA as a modular structure built from a combination of these building blocks and tertiary linkers is beginning to emerge. At the same time, however, more detailed analysis of water, metal, ligand and protein binding to RNA is revealing the effect of these moieties on folding and structure formation. The balance between the views of RNA structure either as strictly a construct of preformed building blocks linked in a limited number of ways or as a flexible polymer assuming a global fold influenced by its environment will be the focus of current and future RNA structural biology.


id: cord-329102-2y49kcwu
title: Structure of the full SARS-CoV-2 RNA genome in infected cells
author: Lan, Tammy C. T.
date: 2020-06-30
txt: ./txt/cord-329102-2y49kcwu.txt
cache: ./cache/cord-329102-2y49kcwu.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.06.29.178343
doi: 10.1101/2020.06.29.178343
summary:
  We evaluated the robustness of our in-cell data derived genome-wide model by varying two critical RNA folding parameters used by RNAstructure: 1) the maximum allowed distance for base pairing and 2) the threshold for DMS signal normalization. Previous studies that computationally predicted genome-wide SARS-Cov-2 RNA structures used 1) RNAz, a thermodynamic-based model that additionally takes sequence alignment and considers base pairing conservation (Gruber et al., 2010; Rangan, Zheludev and Das, 2020) , and 2) Contrafold, which predicts RNA secondary structures without physics-based models and instead uses learned parameters based on known structures (Do, Woods and Batzoglou, 2006) . Interestingly, in silico predictions of the RNA structure of the SARS-CoV-2 genome using RNAz (Rangan, Zheludev and Das, 2020) and ScanFold (Andrews et al., 2020) do not find the 3-stem pseudoknot but instead support our in-cell model of Alternative Stem 1.

abstract:
  SARS-CoV-2 is a betacoronavirus with a single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Currently, there are no antiviral drugs or vaccines with proven efficacy, and development of these treatments are hampered by our limited understanding of the molecular and structural biology of the virus. Like many other RNA viruses, RNA structures in coronaviruses regulate gene expression and are crucial for viral replication. Although genome and transcriptome data were recently reported, there is to date little experimental data on predicted RNA structures in SARS-CoV-2 and most putative regulatory sequences are uncharacterized. Here we report the secondary structure of the entire SARS-CoV-2 genome in infected cells at single nucleotide resolution using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq). Our results reveal previously undescribed structures within critical regulatory elements such as the genomic transcription-regulating sequences (TRSs). Contrary to previous studies, our in-cell data show that the structure of the frameshift element, which is a major drug target, is drastically different from prevailing in vitro models. The genomic structure detailed here lays the groundwork for coronavirus RNA biology and will guide the design of SARS-CoV-2 RNA-based therapeutics.


id: cord-329504-91te3nu8
title: Making the invisible enemy visible
author: Croll, Tristan
date: 2020-10-07
txt: ./txt/cord-329504-91te3nu8.txt
cache: ./cache/cord-329504-91te3nu8.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.10.07.307546
doi: 10.1101/2020.10.07.307546
summary:
  A general indication of how well the atomic model fits the measurement data can be obtained by comparing the deposited R-factors to results from PDB-REDO (10) (including Whatcheck (11)) to determine the overall density fit as well as many other diagnostics. Our remodelled structure is offering a valuable structural basis for future studies, such as in-silico docking and drug design targeting at SARS-CoV-2 RdRp (34), as well as for computational modelling or simulations to investigate the molecular mechanism of viral replication (31, 35, 36) . This has included a number of posts on our homepage aimed at non-scientists and live streaming the reprocessing of data on Twitch, as well as the design, production, and public release of an accurate 3D printed model of SARS-CoV-2 based on deposited structures for use as a prop for outreach activities.

abstract:
  During the COVID-19 pandemic, structural biologists have rushed to solve the structures of the 28 proteins encoded by the SARS-CoV-2 genome in order to understand the viral life cycle and enable structure-based drug design. In addition to the 200 structures from SARS-CoV previously solved, 367 structures covering 16 of the viral proteins have been released in the span of only 6 months. These structural models serve as basis for research worldwide to understand how the virus hijacks human cells, for structure-based drug design and to aid in the development of vaccines. However, errors often occur in even the most careful structure determination - and are even more common among these structures, which were solved under immense pressure. From the beginning of the pandemic, the Coronavirus Structural Taskforce has categorized, evaluated and reviewed all of these experimental protein structures in order to help downstream users and original authors. Our website also offers improved models for many key structures, which have been used by Folding@Home, OpenPandemics, the EU JEDI COVID-19 challenge, and others. Here, we describe our work for the first time, give an overview of common problems, and describe a few of these structures that have since acquired better versions in the worldwide Protein Data Bank, either from new data or as depositor re-versions using our suggested changes.


id: cord-330427-3eoio8uk
title: Structural biology in antiviral drug discovery
author: Bassetto, Marcella
date: 2016-09-06
url: https://doi.org/10.1016/j.coph.2016.08.014
doi: 10.1016/j.coph.2016.08.014
abstract:
  Structural biology has emerged during the last thirty years as a powerful tool for rational drug discovery. Crystal structures of biological targets alone and in complex with ligands and inhibitors provide essential insights into the mechanisms of actions of enzymes, their conformational changes upon ligand binding, the architectures and interactions of binding pockets. Structure-based methods such as crystallographic fragment screening represent nowadays invaluable instruments for the identification of new biologically active compounds. In this context, three-dimensional protein structures have played essential roles for the understanding of the activity and for the design of novel antiviral agents against several different viruses. In this review, the evolution in the resolution of viral structures is analysed, along with the role of crystal structures in the discovery and optimisation of new antivirals.


id: cord-330590-nu8ckeud
title: Viral metacommunities associated to bats and rodents at different spatial scales
author: Nieto-Rabiela, F.
date: 2018-12-30
url: https://www.ncbi.nlm.nih.gov/pubmed/32218712/
doi: 10.1556/168.2018.19.2.9
abstract:
  One of the main goals of community ecology is to measure the relative importance of environmental filters to understand patterns of species distribution at different temporal and spatial scales. Likewise, the identification of factors that shape symbiont metacommunity structures is important in disease ecology because resulting structures drive disease transmission. We tested the hypothesis that distributions of virus species and viral families from rodents and bats are defined by shared responses to host phylogeny and host functional characteristics, shaping the viral metacommunity structures at four spatial scales (Continental, Biogeographical, Zoogeographical, and Regional). The contribution of host phylogeny and host traits to the metacommunity of viruses at each spatial scale was calculated using a redundant analysis of canonical ordering (RDA). For rodents, at American Continental scale the coherence of viral species metacommunity increased while the spatial scale decreased and Quasi-Clementsian structures were observed. This pattern suggests a restricted distribution of viruses through their hosts, while in the Big Mass (Europe, Africa, and Asia), the coherence decreased as spatial scale decreased. Viral species metacommunities associated with bats was dominated by random structures along all spatial scales. We suggest that this random pattern is a result of the presence of viruses with high occupancy range such as rabies (73%) and coronavirus (27%), that disrupt such structures. At viral family scale, viral metacommunities associated with bats showed coherent structures, with the emergence of Quasi- Clementsian and Checkerboard structures. RDA analysis indicates that the assemblage of viral diversity associated with rodents and bats responds to phylogenetic and functional characteristics, which alternate between spatial scales. Several of these variations could be subject to the spatial scale, in spite of this, we could identify patterns at macro ecological scale. The application of metacommunity theory at symbiont scales is particularly useful for large-scale ecological analysis. Understanding the rules of host-virus association can be useful to take better decisions in epidemiological surveillance, control and even predictions of viral distribution and dissemination. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1556/168.2018.19.2.9 and is accessible for authorized users.


id: cord-340554-7cwp2xbw
author: Yamasaki, Satoshi
date: 2019-03-06
txt: ./txt/cord-340554-7cwp2xbw.txt
cache: ./cache/cord-340554-7cwp2xbw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30840170/
doi: 10.1007/s10822-019-00195-y
summary:
  The tertiary structure of RNA molecules and RNA–RNA/protein interaction sites are of increasing importance as potential targets for new medicines that treat a broad array of human diseases. In this report, we present a novel workflow to predict RNA tertiary structures and RNA–RNA/protein interactions using the KNIME environment, which enabled us to assemble a combination of RNA-related analytical tools and databases. The workflow, RNA Structure Prediction, at the top of Fig. 1 models the tertiary structure of the RNA target according to secondary structure information, which is based on the calculated results from CentroidFold [36] . Figure 2c , d show the predicted secondary and tertiary structures for the non-coding RNA (FR000373 of fRNAdb) calculated by the CentroidFold and Rascal nodes. The RNA-protein workflow is presented at the bottom of Fig. 1 and is used to predict the structure of a nucleic acid drug-target protein complex by molecular simulations.

title:
  ToGo-WF: prediction of RNA tertiary structures and RNA–RNA/protein interactions using the KNIME workflow

abstract:
  Recent progress in molecular biology has revealed that many non-coding RNAs regulate gene expression or catalyze biochemical reactions in tumors, viruses and several other diseases. The tertiary structure of RNA molecules and RNA–RNA/protein interaction sites are of increasing importance as potential targets for new medicines that treat a broad array of human diseases. Current RNA drugs are split into two groups: antisense RNA molecules and aptamers. In this report, we present a novel workflow to predict RNA tertiary structures and RNA–RNA/protein interactions using the KNIME environment, which enabled us to assemble a combination of RNA-related analytical tools and databases. In this study, three analytical workflows for comprehensive structural analysis of RNA are introduced: (1) prediction of the tertiary structure of RNA; (2) prediction of the structure of RNA–RNA complexes and analysis of their interactions; and (3) prediction of the structure of RNA–protein complexes and analysis of their interactions. In an RNA–protein case study, we modeled the tertiary structure of pegaptanib, an aptamer drug, and performed docking calculations of the pegaptanib-vascular endothelial growth factor complex using a fragment of the interaction site of the aptamer. We also present molecular dynamics simulations of the RNA–protein complex to evaluate the affinity of the complex by mutating bases at the interaction interface. The results provide valuable information for designing novel features of aptamer-protein complexes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10822-019-00195-y) contains supplementary material, which is available to authorized users.


id: cord-346546-yffwd0dc
title: Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease
author: Douangamath, Alice
date: 2020-05-27
txt: ./txt/cord-346546-yffwd0dc.txt
cache: ./cache/cord-346546-yffwd0dc.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.05.27.118117
doi: 10.1101/2020.05.27.118117
summary:
  To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease. For 113 another series of hit compounds, containing a N-chloroacetyl piperidinyl-4-carboxamide 114 motif (Table S2 ) which displays lower reactivity and were not frequent hitters in previous 115 screens, we attempted crystallization despite their absence of labelling in the stringent 116 The bound fragments comprehensively sample all subsites of the active 287 site revealing diverse expansion vectors, and the electrophiles provide extensive, systematic 288 as well as serendipitous, data for designing covalent compounds. Crystal structure of SARS-CoV-2 main protease 763 provides a basis for design of improved alpha-ketoamide inhibitors

abstract:
  COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. Our crystallographic screen identified 71 hits that span the entire active site, as well as 3 hits at the dimer interface. These structures reveal routes to rapidly develop more potent inhibitors through merging of covalent and non-covalent fragment hits; one series of low-reactivity, tractable covalent fragments was progressed to discover improved binders. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease.


id: cord-346965-0oq2n0af
title: Bridging protein local structures and protein functions
author: Liu, Zhi-Ping
date: 2008-04-18
txt: ./txt/cord-346965-0oq2n0af.txt
cache: ./cache/cord-346965-0oq2n0af.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/18421562/
doi: 10.1007/s00726-008-0088-8
summary:
  The characteristics between interface and noninterface portions of a protein surface, such as sequence conservation, proportions of amino acids, secondary structure, solvent accessibility and side-chain conformational entropy, are often used to distinguish the specificity of local structures relating to protein binding function. The method relies on a simplified representation of the chemical groups found in amino acid side-chains to identify functional sites from a single protein structure and a number of its sequence homologs. (2006) improved previous approaches by combining two known measures of ''functionality'' in proteins, i.e. cleft volume and residue conservation, to develop a method for identifying the location of ligand-binding pockets in proteins. (2006) applied an SVM method to predict DNA-binding sites using the features including amino acid sequence, profile of evolutionary conservation of sequence positions, and low-resolution structural information. (2006) developed a method to predict both protein-protein binding site location and interface type (obligate or non-obligate) using a Bayesian network in combination with surface patch analysis.

abstract:
  One of the major goals of molecular and evolutionary biology is to understand the functions of proteins by extracting functional information from protein sequences, structures and interactions. In this review, we summarize the repertoire of methods currently being applied and report recent progress in the field of in silico annotation of protein function based on the accumulation of vast amounts of sequence and structure data. In particular, we emphasize the newly developed structure-based methods, which are able to identify locally structural motifs and reveal their relationship with protein functions. These methods include computational tools to identify the structural motifs and reveal the strong relationship between these pre-computed local structures and protein functions. We also discuss remaining problems and possible directions for this exciting and challenging area.


id: cord-349839-s32d3di2
title: RNA pseudoknots
author: Westhof, Eric
date: 1992-06-30
txt: ./txt/cord-349839-s32d3di2.txt
cache: ./cache/cord-349839-s32d3di2.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/0959440X9290221R
doi: 10.1016/0959-440x(92)90221-r
summary:
  In the folding of a single-stranded RNA molecule, there are only three ways in which two base-paired segments can be related to each other: two consecutive hairpins; two helices separated by an internal bulge; and, pseudoknots [1]. The first two motifs can be represented as two-dimensional graphs without self-intersections whereas pseudoknots cannot, as they are fundamentally three-dimensional structures in which the four base-paired strands alternate along the sequence of the RNA molecule. The three types of ''classic'' pseudoknots with co-axial stacking of the two base-paired helices and with single-stranded segments crossing the RNA grooves. The third pseudoknot involves the 530 stem-loop structure [19] , which is known to be important for the binding of tRNA to the ribosomal A site [20] , and was recently shown to be essential for ribosomal function [21.o] .

abstract:
  Abstract RNA pseudoknots result from Watson-Crick base pairing involving a stretch of bases located between paired strands and a distal single-stranded region. Recently, significant advances in our understanding of their structural and functional aspects have been accomplished. At the structural level, modelling and NMR studies have shown that a defined subset of pseudoknots may be considered as tertiary motifs in RNA foldings. At the functional level, there is evidence that the realm of functions encompassed by RNA pseudoknots extends from the control of translation in prokaryotes, retroviruses and coronaviruses to the control of catalytic activity in ribozymes and the control of replication in some plant viruses.


id: cord-351222-9bfchw4u
title: Virtual screening for the discovery of bioactive natural products
author: Rollinger, Judith M.
date: 2008
txt: ./txt/cord-351222-9bfchw4u.txt
cache: ./cache/cord-351222-9bfchw4u.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/18084917/
doi: 10.1007/978-3-7643-8117-2_6
summary:
  Some examples using high throughput docking as a structure-based virtual screening tool will be given here: Liu and Zhou applied a theoretical approach to find natural ligands as potential inhibitors of the SARS-CoV protease, a virus target of the severe acute respiratory syndrome [35] . Barreca and co-authors developed a 3D structure-based pharmacophore model with LIGANDSCOUT for the discovery of new scaffolds acting as HIV-1 non-nucleoside reverse transcriptase inhibitors by virtual screening of large chemical databases. Based on the co-crystal structure of AChE with its ligand galanthamine, a structure-based pharmacophore model was generated and used for an in silico screening of a multi-conformational database consisting of more than 110,000 NPs. From the obtained hit list, promising, virtually active candidates were selected, namely scopoletin (7) and its glucoside scopolin (8) .

abstract:
  In this survey the impact of the virtual screening concept is discussed in the field of drug discovery from nature. Confronted by a steadily increasing number of secondary metabolites and a growing number of molecular targets relevant in the therapy of human disorders, the huge amount of information needs to be handled. Virtual screening filtering experiments already showed great promise for dealing with large libraries of potential bioactive molecules. It can be utilized for browsing databases for molecules fitting either an established pharmacophore model or a three dimensional (3D) structure of a macromolecular target. However, for the discovery of natural lead candidates the application of this in silico tool has so far almost been neglected. There are several reasons for that. One concerns the scarce availability of natural product (NP) 3D databases in contrast to synthetic libraries; another reason is the problematic compatibility of NPs with modern robotized high throughput screening (HTS) technologies. Further arguments deal with the incalculable availability of pure natural compounds and their often too complex chemistry. Thus research in this field is time-consuming, highly complex, expensive and ineffective. Nevertheless, naturally derived compounds are among the most favorable source of drug candidates. A more rational and economic search for new lead structures from nature must therefore be a priority in order to overcome these problems. Here we demonstrate some basic principles, requirements and limitations of virtual screening strategies and support their applicability in NP research with already performed studies. A sensible exploitation of the molecular diversity of secondary metabolites however asks for virtual screening concepts that are interfaced with well-established strategies from classical pharmacognosy that are used in an effort to maximize their efficacy in drug discovery. Such integrated virtual screening workflows are outlined here and shall help to motivate NP researchers to dare a step towards this powerful in silico tool.


id: cord-354465-5nqrrnqr
title: RNA structures with pseudo-knots: Graph-theoretical, combinatorial, and statistical properties
author: Haslinger, Christian
date: 1999
txt: ./txt/cord-354465-5nqrrnqr.txt
cache: ./cache/cord-354465-5nqrrnqr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17883226/
doi: 10.1006/bulm.1998.0085
summary:
  Numerical studies based on kinetic folding and a simple extension of the standard energy model show that the global features of the sequence-structure map of RNA do not change when pseudo-knots are introduced into the secondary structure picture. Numerical studies based on kinetic folding and a simple extension of the standard energy model show that the global features of the sequence-structure map of RNA do not change when pseudo-knots are introduced into the secondary structure picture. In case of one particular class of biopolymers, the ribonucleic acid (RNA) molecules, decoding of information stored in the sequence can be properly decomposed into two steps: (i) formation of the secondary structure, that is, of the pattern of Watson-Crick (and GU) base pairs, and (ii) the embedding of the contact structure in three-dimensional space. On the other hand, an increasing number of experimental findings, as well as results from comparative sequence analysis, suggest that pseudo-knots are important structural elements in many RNA molecules (Westhof and Jaeger, 1992) .

abstract:
  The secondary structures of nucleic acids form a particularly important class of contact structures. Many important RNA molecules, however, contain pseudo-knots, a structural feature that is excluded explicitly from the conventional definition of secondary structures. We propose here a generalization of secondary structures incorporating ‘non-nested’ pseudo-knots, which we call bi-secondary structures, and discuss measures for the complexity of more general contact structures based on their graph-theoretical properties. Bi-secondary structures are planar trivalent graphs that are characterized by special embedding properties. We derive exact upper bounds on their number (as a function of the chain length n) implying that there are fewer different structures than sequences. Computational results show that the number of bi-secondary structures grows approximately like 2.35(n). Numerical studies based on kinetic folding and a simple extension of the standard energy model show that the global features of the sequence-structure map of RNA do not change when pseudo-knots are introduced into the secondary structure picture. We find a large fraction of neutral mutations and, in particular, networks of sequences that fold into the same shape. These neutral networks percolate through the entire sequence space.


id: cord-355327-d3gcfepx
title: Conformational changes in redox pairs of protein structures
author: Fan, Samuel W
date: 2009-08-01
txt: ./txt/cord-355327-d3gcfepx.txt
cache: ./cache/cord-355327-d3gcfepx.txt
extension: .txt
mime: text/plain
url: http://europepmc.org/articles/pmc2776962?pdf=render
doi: 10.1002/pro.175
summary:
  Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. These groups were: proteins that oxidize disulfides following expulsion of metals such as Zn; proteins that exhibited major reorganization or ''''morphing'''' of portions of the polypeptide backbone in association with disulfide redox-activity; proteins that exhibited order/disorder transitions; and proteins that exhibited changes in quaternary structure. Twenty-nine Redox Pair protein clusters with intermolecular disulfide bonds exhibit changes in quaternary structure upon oxidation/reduction. We were previously aware of two instances where subdomain morphing of proteins has been associated with reversible disulfide reduction: a redox-controlled structural reorganization of the ion channel CLIC1 proposed to regulate its insertion into membranes, 18 and sequential oxidation of the transcription factor OxyR in response to oxidative stress which modulates its quaternary structure and DNA-binding properties.

abstract:
  Disulfides are conventionally viewed as structurally stabilizing elements in proteins but emerging evidence suggests two disulfide subproteomes exist. One group mediates the well known role of structural stabilization. A second redox-active group are best known for their catalytic functions but are increasingly being recognized for their roles in regulation of protein function. Redox-active disulfides are, by their very nature, more susceptible to reduction than structural disulfides; and conversely, the Cys pairs that form them are more susceptible to oxidation. In this study, we searched for potentially redox-active Cys Pairs by scanning the Protein Data Bank for structures of proteins in alternate redox states. The PDB contains over 1134 unique redox pairs of proteins, many of which exhibit conformational differences between alternate redox states. Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. Based on evidence gathered supporting disulfide redox activity, we propose disulfides present in alternate redox states are likely to have physiologically relevant redox activity.


