Evolution of drug resistance drives destabilization of flap region dynamics in HIV-1 protease.

ABSTRACT: The HIV-1 protease is one of several common key targets of combination drug therapies for human immunodeficiency virus infection and acquired immunodeficiency syndrome. During the progression of the disease, some individual patients acquire drug resistance due to mutational hotspots on the viral proteins targeted by combination drug therapies. It has recently been discovered that drug-resistant mutations accumulate on the "flap region" of the HIV-1 protease, which is a critical dynamic region involved in nonspecific polypeptide binding during invasion and infection of the host cell. In this study, we utilize machine learning-assisted comparative molecular dynamics, conducted at single amino acid site resolution, to investigate the dynamic changes that occur during functional dimerization a

SUBMITTER: Rajendran M 

PROVIDER: S-EPMC10469570 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature