Proposal of pharmacophore model for HIV reverse transcriptase inhibitors: Combined mutational effect analysis, molecular dynamics, molecular docking and pharmacophore modeling study.

ABSTRACT:

Objectives

Antiretroviral therapy (ART) efficacy is jeopardized by the emergence of drug resistance mutations in HIV, compromising treatment effectiveness. This study aims to propose novel analogs of Effavirenz (EFV) as potential direct inhibitors of HIV reverse transcriptase, employing computer-aided drug design methodologies.

Methods

Three key approaches were applied: a mutational profile study, molecular dynamics simulations, and pharmacophore development. The impact of mutations on the stability, flexibility, function, and affinity of target proteins, especially those associated with NRTI, was assessed. Molecular dynamics analysis identified G190E as a mutation significantly altering protein properties, potentially leading to therapeutic failure. Comparative analysis rev

SUBMITTER: Annan A 

PROVIDER: S-EPMC10832406 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature