Divide-and-conquer-based quantum chemical study for interaction between HIV-1 reverse transcriptase and MK-4965 inhibitor

Patchreenart Saparpakorn, Masato Kobayashi, Supa Hannongbua, Hiromi Nakai*

*この研究の対応する著者

研究成果: Article査読

8 被引用数 (Scopus)

抄録

MK-4965, 3-{5-[(6-Amino-1H-pyrazolo[3,4-b]pyridine-3-yl)methoxy]-2- chlorophenoxy}-5-chloro-benzonitrile, is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) revealing high levels of potency against wild-type (WT) the human immunodeficiency virus type-1 (HIV-1) and some important mutants. The divide-and-conquer (DC) based Hartree-Fock (HF) and second-order Møller-Plesset perturbation theory (MP2) calculations were performed for the binding modes of MK-4965 in the reverse transcriptase (RT) of the WT HIV-1 and a mutant Y181C, 181 tyrosine mutated by cysteine. The binding pockets of MK-4965 consisting of 19 residues are selected for the study. Numerical assessments confirmed the efficiency and accuracy of the DC-MP2 method in comparison with the conventional MP2 one. Subsystem interaction energies obtained by the DC-MP2 calculations clarified the key parts of the binding between MK-4965 and HIV-1: hydrogen bonding with 102 lysine, which is apart from mutated 181 residue. The present information can give a helpful guide for the future inhibitor design.

本文言語English
ページ(範囲)510-517
ページ数8
ジャーナルInternational Journal of Quantum Chemistry
113
4
DOI
出版ステータスPublished - 2013 2 15

ASJC Scopus subject areas

  • 原子分子物理学および光学
  • 凝縮系物理学
  • 物理化学および理論化学

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