Resistance mechanism of human immunodeficiency virus type-1 protease to inhibitors: A molecular dynamic approach.

ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) protease inhibitors comprise an important class of drugs used in HIV treatments. However, mutations of protease genes accelerated by low fidelity of reverse transcriptase yield drug resistant mutants of reduced affinities for the inhibitors. This problem is considered to be a serious barrier against HIV treatment for the foreseeable future. In this study, molecular dynamic simulation method was used to examine the combinational and additive effects of all known mutations involved in drug resistance against FDA approved inhibitors. Results showed that drug resistant mutations are not randomly distributed along the protease sequence; instead, they are localized on flexible or hot points of the protein chain. Substitution of more hydrophobic residue

SUBMITTER: Dayer MR 

PROVIDER: S-EPMC5019311 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature