Poster Presentation 2014 International Biophysics Congress

The study on interaction between HIV-1 protease and C2-symmetric inhibitors by computational methods (#677)

Guodong Hu 1 , Qianjun Liu 1 , Shuhua Shi 2 , Jihua Wang 1
  1. Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Dezhou University, Dezhou, China
  2. College of Science, Shandong Jianzhu University, Jinan, China

The human immunodeficiency virus type 1 protease (HIV-1 PR) is a major target for the design of anti-AIDS drugs. Some C2-symmetric inhibitors were designed for the C2-symmetric binding pocket of HIV-1 PR. The crystallographic structures reveal that the binding modes are not C2-symmetric for C2- symmetric inhibitors binding to PR. In this work, four molecular dynamics (MD) simulations were performed to investigate the binding modes between four C2-symmetric inhibitors (6AD, 6AG, 6FD and 6FG) and PR, as well as the stabilities of these inhibitors in binding pocket. The analysis of hydrophobic surface of the binding pocket shows that it is necessary to add polar group on P1 and P2 of the inhibitors. The analysis of hydrogen bonds formed between inhibitors and residues (Asp25/Asp25', Ile50/Ile50') indicates that the steric structures of inhibitors are not suitable for the binding pocket. The two increased polar groups of trifluoromethyl and formamido meet the need of the binding pocket to polar molecules. The inhibitor with these two groups (6FG) has stronger stability than the other three inhibitors with only one group or not. The rank of binding free energies calculated by Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) method agrees well with the experimental data. It is expected that this study can provide theoretical guidance for the designs of anti-AIDS drugs targeting HIV-1 PR.