Title

Decomposing the energetic impact of drug-resistant mutations: the example of HIV-1 protease-DRV binding

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

2012-1

Document Type

Book Chapter

Subjects

Crystallography, X-Ray; Drug Resistance, Viral; HIV Protease; HIV Protease Inhibitors; HIV-1; Humans; Molecular Dynamics Simulation; Mutation; Sulfonamides; Thermodynamics

Disciplines

Biochemistry, Biophysics, and Structural Biology | Molecular Biology | Pharmacology, Toxicology and Environmental Health

Abstract

HIV-1 protease is a major drug target for AIDS therapy. With the appearance of drug-resistant HIV-1 protease variants, understanding the mechanism of drug resistance becomes critical for rational drug design. Computational methods can provide more details about inhibitor-protease binding than crystallography and isothermal titration calorimetry. The latest FDA-approved HIV-1 protease inhibitor is Darunavir (DRV). Herein, each DRV atom is evaluated by free energy component analysis for its contribution to the binding affinity with wild-type protease and ACT, a drug-resistant variant. This information can contribute to the rational design of new HIV-1 protease inhibitors.

DOI of Published Version

10.1007/978-1-61779-465-0_32

Source

Methods Mol Biol. 2012;819:551-60. Link to article on publisher's site

Journal/Book/Conference Title

Methods in molecular biology (Clifton, N.J.)

Related Resources

Link to Article in PubMed

PubMed ID

22183557

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