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Validation of a Model for the Complex of HIV-1 Reverse Transcriptase with Nonnucleoside Inhibitor TMC125

Marina Udier-Blagović, Julian Tirado-Rives, and William L. Jorgensen*

Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107

J. Am. Chem. Soc., 2003, 125 (20), pp 6016–6017

DOI: 10.1021/ja034308c

Publication Date (Web): April 25, 2003

Abstract

The structure for the complex of nonnucleoside inhibitor TMC125 and HIV-1 reverse transcriptase has been determined and validated through computation of resistance profiles using Monte Carlo/free-energy perturbation calculations. The good quantitative agreement between the computed and experimental anti-HIV activities for TMC125, nevirapine, and efavirenz with wild-type RT and four common mutants (L100I, K103N, Y181C, and Y188L) confirms the correctness of the predicted structure and provides insights into the improved potency of this novel NNRTI. The blue shading in the figure indicates basic residues.

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PDB: 1ep4

History

Published In Issue May 21, 2003
Received January 23, 2003

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Communication

Validation of a Model for the Complex of HIV-1 Reverse Transcriptase with Nonnucleoside Inhibitor TMC125

Abstract

Tools

SciFinder Links

Accession Codes

History

Recommend & Share

Related Content

Roles of Conformational and Positional Adaptability in Structure-Based Design of TMC125-R165335 (Etravirine) and Related Non-nucleoside Reverse Transcriptase Inhibitors That Are Highly Potent and Effective against Wild-Type and Drug-Resistant HIV-1 Variants

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