Molecular dynamics simulations of metalloproteinases types 2 and 3 reveal differences in the dynamic behavior of the S1' binding pocket.
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.
de Oliveira
Cesar Augusto F
CA
Howard Hughes Medical Institute, Center for Theoretical Biological Physics, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA.
Zissen
Maurice
M
Mongon
John
J
McCammon
J Andrew
JA
D001665:Binding Sites; D003198:Computer Simulation; D017076:Computer-Aided Design; D003461:Crystallography; D015195:Drug Design; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008956:Models, Chemical; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000379:methods*
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2