Theoretical investigation on nevirapine and HIV-1 reverse transcriptase binding site interaction, based on ONIOM method

被引：68

作者：

Kuno, M

Hannongbua, S ^{[1
]}

Morokuma, K

机构：

[1] Kasetsart Univ, Fac Sci, Dept Chem, Bangkok 10900, Thailand

[2] Emory Univ, Dept Chem, Atlanta, GA 30323 USA

[3] Emory Univ, Cherry L Emerson Ctr Sci Computat, Atlanta, GA 30323 USA

来源：

CHEMICAL PHYSICS LETTERS | 2003年 / 380卷 / 3-4期

关键词：

D O I：

10.1016/j.cplett.2003.09.030

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

The ONIOM method was applied to the interaction of nevirapine with the HIV-1 reverse transcriptase binding site. The isolated complex of pyridine (part of nevirapine) and methyl phenol (part of Tyr181) was found at the MP2/631+G(d) level to have stacking interaction with 8.8 kcal/mol binding energy. Optimization of nevirapine and Tyr181 geometry in the pocket of 16 amino acid residues at the ONIOM3(MP2/6-31G(d):HF/3-21G:PM3) level gave the complex structure with weak hydrogen bonding but without stacking interaction. The binding energy of 8.9 kcal/mol comes almost entirely from the interaction of nevirapine with amino acid residues other than Tyr181. (C) 2003 Elsevier B.V. All rights reserved.

引用

页码：456 / 463

页数：8

共 24 条

[1] The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages [J].