2. Academic Validation
  3. Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase

Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase

  • Bioorg Med Chem Lett. 2006 Feb;16(3):663-7. doi: 10.1016/j.bmcl.2005.10.038.
William L Jorgensen 1,  Juliana Ruiz-Caro,  Julian Tirado-Rives,  Aravind Basavapathruni,  Karen S Anderson,  Andrew D Hamilton
Affiliations

Affiliation

  • 1 Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA. william.jorgensen@yale.edu
PMID: 16263277 DOI: 10.1016/j.bmcl.2005.10.038
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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