key: cord-0024340-6uap1s9q
authors: Kumar, Amit; Vashisth, Harish
title: Conformational dynamics and energetics of viral RNA recognition by lab-evolved proteins
date: 2021-10-29
journal: nan
DOI: 10.1039/d1cp03822b
sha: 441a83ad6f257ddc4051cede6b8de159dbb1fb11
doc_id: 24340
cord_uid: 6uap1s9q

The conserved and structured elements in viral RNA genomes interact with proteins to regulate various events in the viral life cycle and have become key targets for developing novel therapeutic approaches. We probe physical interactions between lab-evolved proteins and a viral RNA element from the HIV-1 genome. Specifically, we study the role of an arginine-rich loop in recognition of designed proteins by the viral RNA element. We report free energy calculations to quantitatively estimate the protein/RNA binding energetics, focusing on the mutations of arginine residues involved in recognition of the major groove of RNA by proteins.

………………………………………………………………………………. S3 Table S2 ………………………………………………………………………………. S4 Table S3 ………………………………………………………………………………. S4 Table S4 ………………………………………………………………………………. S5 Table S5 ………………………………………………………………………………. S5 Table S6 ………………………………………………………………………………. S6 Table S7 ………………………………………………………………………………. S7 Table S8 ………………………………………………………………………………. S7 Table S9 ………………………………………………………………………………. S8 Table S10 ………………………………………………………………………………. S8 P1/TAR  47968  9  42  42  P2/TAR  47959  10  42  43  P3/TAR  47927  10  42  43  P4/TAR  47939  9  42  42  Table S2 : Free energy data for single mutations in the TBP variant P1. The computed free energy changes upon R47A, R49A, and R50A mutations of P1 in solution (∆G free ) and in complex (∆G comp ) with TAR. The relative binding free energy (∆∆G) for each mutation is reported in the last column. The fractional occupancy is the fraction of simulation frames, sampled at 1 ns, in which a specific interaction is occupied. We determined the hydrogen bond occupancy using a cutoff of 3.5 Å for heavy atoms (oxygen and nitrogen). 

Snapshots similar to Fig. S8 are shown for the R47A-R49A-R52A (R50A in case of P1) mutations in TBP-TAR complexes