Studies on the Binding Modes of HIV-1 Integrase with Viral DNA via Molecular Docking Method

Chem. J. Chinese Universities

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Studies on the Binding Modes of HIV-1 Integrase with Viral DNA via Molecular Docking Method

HU Jian-Ping^1,2, KE Guo-Tao¹, CHANG Shan¹, CHEN Wei-Zu¹, WANG Cun-Xin¹*

1. College of Life Science and Biological Bioengineering, Beijing University of Technology, Beijing 100022, China;
2. Department of Chemistry and Life Science, Leshan Normal University, Leshan 614004, China

Received:2007-09-21 Revised:1900-01-01 Online:2008-07-10 Published:2008-07-10
Contact: WANG Cun-Xin

Abstract

Abstract: HIV-1 integrase(IN) integrates the viral DNA into the host cell chromosome, however, the binding mode of IN with the viral DNA and the integration mechanism remain unclear. In this paper, molecular docking method was used to investigate the interactions of HIV-1 IN dimer with the 8 bp and 27 bp segments of viral DNA before the 3’ processing(3’-P) reaction, and the specific binding mode between IN and its substrate 27 bp segments of viral DNA was obtained. The results show that IN has one specific DNA-binding region and another non-specific DNA-binding region. The key residues for IN dimer binding with viral DNA are K14, R20, K156, K159, K160, K186, K188, R199 residues in chain B and K219, W243, K244, R262, R263 residues in chain A. The explanation for the minimum length of 15 bp viral DNA to activate IN was given on the basis of the docked complex structure. Through the analysis of the binding energy, it was found that non-polar interactions are the principal factor favoring the binding between IN and DNA; whereas, the stable association of viral DNA with the key residues are mainly driven by polar interactions. The simulation results basically agree with the experimental data, which provide us with some structural information for the drug design on the basis of the structure of HIV-1 IN.

Key words: HIV-1 integrase, Viral DNA, Molecular docking, Binding mode, Drug molecule design

CLC Number:

O641

TrendMD:

HU Jian-Ping^1,2, KE Guo-Tao¹, CHANG Shan¹, CHEN Wei-Zu¹, WANG Cun-Xin¹*. Studies on the Binding Modes of HIV-1 Integrase with Viral DNA via Molecular Docking Method[J]. Chem. J. Chinese Universities, doi: .

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Studies on the Binding Modes of HIV-1 Integrase with Viral DNA via Molecular Docking Method

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