doi: 10.1016/j.bmcl.2005.10.038.
Epub 2005 Nov 2.
Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase
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- PMID: 16263277
- DOI: 10.1016/j.bmcl.2005.10.038
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Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase
Bioorg Med Chem Lett.
2006 Feb.
Abstract
Design principles are delineated for non-nucleoside inhibitors for HIV-1 reverse transcriptase (NNRTIs). Simultaneous optimization of binding affinity for wild-type RT, tolerance for viral mutations, and physical properties is pursued. Automated lead generation with the growing program BOMB, Monte Carlo simulations with free-energy perturbation theory for lead optimization, and property analysis with QikProp are featured. An initial 30 microM lead has been optimized rapidly to the 10 nM level.
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