Molecular Dynamics Simulations of Metalloproteinases Types 2 and 3 Reveal Differences in the Dynamic Behavior of the S1' Binding Pocket

Authors: de Oliveira, Cesar Augusto F.¹; Zissen, Maurice¹; Mongon, John¹; Mccammon, J. A.¹

Source: Current Pharmaceutical Design, Volume 13, Number 34, December 2007 , pp. 3471-3475(5)

Publisher: Bentham Science Publishers

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Abstract:

Matrix Metalloproteinases (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 Metalloproteinases type 2 (MMP-2), also known as gelatinase A, has been identified in a numbers of cancer metastases. 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 S1' 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.

Keywords: Matrix metalloproteinse; molecular dynamics; S1' binding pocket; MMP-2; MMP-3; metalloproteinase inhibitor

Document Type: Research article

DOI: 10.2174/138161207782794211

Affiliations: 1: Howard Hughes Medical Institute, Center for Theoretical Biological Physics, Department of Chemistry and Biochemistry, Department of Pharmacology, University of California at San Diego, La Jolla, California 2093, USA.