Molecular dynamics simulations applied to the study of subtypes of HIV-1 protease common to Brazil, Africa, and Asia

被引：0
作者：
Paulo R. Batista
Alan Wilter
Elza H. A. B. Durham
Pedro G. Pascutti
机构：
[1] Universidade Federal do Rio de Janeiro,Laboratório de Modelagem e Dinâmica Molecular, Instituto de Biofisica Carlos Chagas Filho
[2] Laboratório Nacional de Computação Cientifica,Instituto de Matemática e Estatistica
[3] Instituoo Ludwig de Pesquisa sobre o Câncer,undefined
[4] Universidade São Paulo,undefined
来源：
Cell Biochemistry and Biophysics | 2006年 / 44卷
关键词：
Molecular Dynamics; Gromacs; HIV-1 protease; ritonavir; subtypes; non-B; modelling; free energy; LIE;
D O I：
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中图分类号：
学科分类号：
摘要：
Africa accounts for the majority of HIV-1 infections worldwide caused mainly by the A and C viral subtypes rather than B subtype, which prevails in the United States and Western Europe. In Brazil, B subtype is the major subtype, but F, C, and A also circulate. These non-B subtypes present polymorphisms, and some of them occur at sites that have been associated with drug resistance, including the HIV-1 protease (PR), one important drug target. Here, we report a Molecular Dynamics study of the B and non-B PR complexed with the inhibitor ritonavir to delineate the behavior of each subtype. We compare root mean squared deviation, binding free energy by linear interaction energy approach, hydrogen bonds, and intermolecular contact surface area between inhibitor and PR. From our results, we can provide a basis to understand the molecular mechanism of drug resistance in non-B subtypes. In this sense, we found a decrease of approx 4 kcal/mol in ΔG of binding between B and non-B subtypes. This corresponds to the loss of one hydrogen bond, which is in agreement with our H-bond analysis. Previous experimental affinity studies reported analogous results with inhibition constant values for non-B PR.
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页码：395 / 404
页数：9
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