Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1367643 | Bioorganic & Medicinal Chemistry Letters | 2006 | 5 Pages |
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 μM lead has been optimized rapidly to the 10 nM level.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
William L. Jorgensen, Juliana Ruiz-Caro, Julian Tirado-Rives, Aravind Basavapathruni, Karen S. Anderson, Andrew D. Hamilton,