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

doi:10.1016/j.bmcl.2005.10.038

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

Chemistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	663-667
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2005.10.038
State	Published - Feb 1 2006

Keywords

Anti-HIV drugs
Computer-aided drug design
NNRTI
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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10.1016/j.bmcl.2005.10.038

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Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase. / Jorgensen, William L.; Ruiz-Caro, Juliana; Tirado-Rives, Julian; Basavapathruni, Aravind; Anderson, Karen S.; Hamilton, Andrew D.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 3, 01.02.2006, p. 663-667.

Research output: Contribution to journal › Article › peer-review

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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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AU - Basavapathruni, Aravind

AU - Anderson, Karen S.

AU - Hamilton, Andrew D.

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

Abstract

Keywords

ASJC Scopus subject areas

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