id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-338589-1ent68fx	Stoddard, Shana V.	Optimization Rules for SARS-CoV-2 M(pro) Antivirals: Ensemble Docking and Exploration of the Coronavirus Protease Active Site	2020-08-26		.txt	text/plain	11437	606	55	The ensemble docking and characterization work described in this article demonstrates the multifaceted features of the SARS-CoV-2 M(pro) active site, molecular guidelines to improving binding affinity, and ultimately the optimization of drug candidates. After optimization efforts using the design guidelines developed from the molecular docking studies, the average docking score of the parent compounds was improved by 6.59 −log(10)(Kd) in binding affinity which represents an increase of greater than six orders of magnitude. The results of molecular dynamic (MD) simulation of cinanserin-optimized compounds CM02, CM06, and CM07 revealed that CM02 and CM06 fit well into the active site of SARS-CoV-2 M(pro) [Protein Data Bank (PDB) accession number 6LU7] and formed strong and stable interactions with the key residues, Ser-144, His-163, and Glu-166. The use of multiple conformations when using docking will assist in the prediction of new antivirals agents targeting SARS-CoV-2 M pro as the diversity of accessible variations can produce distinct binding poses for an inhibitor compound.	./cache/cord-338589-1ent68fx.txt	./txt/cord-338589-1ent68fx.txt