Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease.

ABSTRACT: Enzyme targets in rapidly replicating systems, such as retroviruses, commonly respond to drug-selective pressure with mutations arising in the active site pocket that limit inhibitor effectiveness by introducing steric hindrance or by eliminating essential molecular interactions. However, these primary mutations are disposed to compromising pathogenic fitness. Emerging secondary mutations, which are often found outside of the binding cavity, may or can restore fitness while maintaining drug resistance. The accumulated drug pressure selected mutations could have an indirect effect in the development of resistance, such as altering protein flexibility or the dynamics of protein-ligand interactions. Here, we show that accumulation of mutations in a drug-resistant HIV-1 protease (HIV-1 PR) var

SUBMITTER: de Vera IM 

PROVIDER: S-EPMC3851887 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature