Structural and binding insights into HIV-1 protease and P2-ligand interactions through molecular dynamics simulations, binding free energy and principal component analysis.

ABSTRACT: HIV-1 protease (HIV-1-pr) plays an important role in viral replication and maturation, making it one of the most attractive targets for anti-retroviral therapy. To design new effective inhibitors able to combat drug resistance in mutant HIV-1-pr variants, it is essential to gain further understanding about the mechanisms by which the recently proposed inhibitors deactivate the mutant HIV-1-pr variants. In the present work, we explored the interactions between two P2-ligands (DRV, and one new derivative, 4UY) with wild type (WT) and two multiple mutant HIV-1-pr variants (p20 and p51) with all atom molecular dynamics (MD) simulations, binding free energy calculations, and principal component analysis (PCA). The trajectories of MD simulations show that both 4UY and DRV primarily bind with the

SUBMITTER: Karnati KR 

PROVIDER: S-EPMC6732013 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature