Elucidating the inhibition mechanism of HIV-1 non-nucleoside reverse transcriptase inhibitors through multicopy molecular dynamics simulations.

ABSTRACT: Human immunodeficiency virus-1 reverse transcriptase (RT) inhibition is a major focus of current anti-AIDS drug discovery and development programs, comprising 17 of the 31 Food and Drug Administration-approved compounds. The emergence of the non-nucleoside RT inhibitor (NNRTI) class of compounds provides a highly specific and structurally diverse set of drugs, which act noncompetitively to perturb normal RT function. Despite a relatively rich set of crystallographic data of RT in various states, details of the allosteric modulation of RT dynamics by NNRTIs are lacking. Capturing this inhibitory mechanism could fuel the design of more effective inhibitors at the NNRTI site and also drive the identification of novel allosteric sites. To address this, we have performed multicopy molecular dyn

SUBMITTER: Ivetac A 

PROVIDER: S-EPMC2744402 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature