Pathway Specific Unbinding Free Energy Profiles of Ritonavir Dissociation from HIV-1 Protease.

ABSTRACT: Investigation of protein-drug recognition is key to understanding drug selectivity and binding affinity. In combination, the binding/unbinding free energy landscape and intermolecular interactions can be used to understand drug binding/unbinding mechanisms. This information is vital for the development of drugs with improved efficacy and explanation of mutation effects. This study investigated the dissociation processes of ritonavir unbinding from HIV protease (HIVp). Analyzing unbinding trajectories modeled by accelerated molecular dynamics (MD) simulations, three distinct pathways, pathways A-C, were characterized. Using a reduced dimensionality strategy with the principal component analysis, we carried out short classical MD runs with explicit water to sample local fluctuation during ri

SUBMITTER: Vig E 

PROVIDER: S-EPMC11844232 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature