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

William L. Jorgensen, Juliana Ruiz-Caro, Julian Tirado-Rives, Aravind Basavapathruni, Karen S. Anderson, Andrew D. Hamilton

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)663-667
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number3
StatePublished - Feb 1 2006


  • Anti-HIV drugs
  • Computer-aided drug design
  • Structure-based drug design

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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