Molecular dynamics simulations of metalloproteinases types 2 and 3 reveal differences in the dynamic behavior of the S1′ binding pocket

被引：9

作者：

de Oliveira, Cesar Augusto F. ^{[1
]}

Zissen, Maurice ^{[1
]}

Mongon, John ^{[1
]}

Mccammon, J. Andrew ^{[1
]}

机构：

[1] Univ Calif San Diego, Howard Hughes Med Inst, Ctr Theoret Biol Phys, Dept Chem & Biochem,Dept Pharmacol, La Jolla, CA 92093 USA

来源：

CURRENT PHARMACEUTICAL DESIGN | 2007年 / 13卷 / 34期

关键词：

Matrix metalloproteinse; molecular dynamics; Sl ' binding pocket; MMP-2; MMP-3; metalloproteinase inhibitor;

D O I：

10.2174/138161207782794211

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Matrix Metalloprotemases (MMPs) are zinc-containing proteinases that are responsible for the metabolism of extracellular matrix proteins. Overexpression of MMPs has been associated with a wide range of pathological diseases such as arthritis, cancer, Multiple sclerosis and Alzheimer's disease. The excessive and unregulated activity of Matrix Metal loprotemases type 2 (MMP-2), also known as gelatinase A, has been identified in a numbers of cancer inetastases. Several MMP inhibitors (MMPi) have been proposed in the literature aiming to interfere in the MMPs activity. In this work we performed long MD simulations in order to study the dynamical behavior of the binding pocket S P in the apo forms of MMP type 2 and 3, and identify, at the molecular level, the structural properties relevant for the designing of specific inhibitor of MMP-2.

引用

页码：3471 / 3475

页数：5

共 37 条

[1] Molecular dynamics: Survey of methods for simulating the activity of proteins [J].