A coarse grained model for the dynamics of flap opening in HIV-1 protease

被引：100

作者：

Tozzini, V

McCammon, JA

机构：

[1] Scuola Normale Super Pisa, NEST, I-56126 Pisa, Italy

[2] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA

来源：

CHEMICAL PHYSICS LETTERS | 2005年 / 413卷 / 1-3期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

D O I：

10.1016/j.cplett.2005.07.075

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：

A coarse grained model for proteins is developed and applied to HIV-1 protease. Molecular dynamics simulations on the tsec timescale and the use of a flexible force field allow study of the opening of the 'flaps' protecting the active site. The opening mechanism reveals peculiar features that might be involved in the substrate capture. An allosteric inhibition effect is demonstrated in specific regions of the protein. This study indicates alternative conformations and target sites to be used as basis for the design of novel inhibitor drugs. (c) 2005 Elsevier B.V. All rights reserved.

引用

页码：123 / 128

页数：6

共 27 条

[1] NON-INTERACTING LOCAL-STRUCTURE MODEL OF FOLDING AND UNFOLDING TRANSITION IN GLOBULAR-PROTEINS .2. APPLICATION TO TWO-DIMENSIONAL LATTICE PROTEINS [J].