title: Structural and energetic analysis on the complexes of clinically isolated subtype C HIV-1 proteases and approved inhibitors by molecular dynamics simulation.
abstract: HIV-1 has a large genetic diversity. Subtype B HIV-1 is commonly found in patients in developed countries. In contrast, an increasing number of patients are infected with the non-B subtype viruses, especially with subtype C HIV-1, in developing countries. It remains to be clarified how mutations or polymorphisms in non-B subtype HIV-1 influence the efficacy of the approved inhibitors. In this study, we have performed molecular dynamics simulations on clinically isolated subtype C HIV-1 proteases in complex with three kinds of approved inhibitors. From the structural and energetic viewpoints, we identified the polymorphisms influencing on the binding of the inhibitors. The effect of the V82I mutation on the association with chemicals and the reason for rare appearance of the D30N mutation in subtype C HIV-1 were discussed in terms of the change of geometry of the residues in HIV-1 protease.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
authors.forename: Shou
authors.initials: S
authors.lastname: Matsuyama
authors.forename: Ay
authors.initials: A
authors.lastname: Aydan
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ode
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hata
authors.forename: Wataru
authors.initials: W
authors.lastname: Sugiura
authors.forename: Tyuji
authors.initials: T
authors.lastname: Hoshino
mesh_terms: D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D014644:Genetic Variation; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009154:Mutation; D013816:Thermodynamics
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1