COMP 338 |
| Matrix metalloproteinases (MMPs) are a highly homologous family of enzymes implicated in a broad variety of disease including cancer. Despite the initial excitement offered by first generation anti-cancer MMP inhibitors, little or no clinical efficacy was observed in human trials. In hindsight, and at least in part, the disappointing results are now thought to be a consequence of the fact that first generation inhibitors were too broad spectrum. In this study, we are using computational methods to investigate what drives binding for a recently reported series of compounds highly selective for MMP-13. Molecular dynamics simulations, binding free energy calculations, and other analysis are being used to characterize the predominant factors which drive ligand association in this system. A comparison of the results obtained from continuum (GB-MD) versus explicit solvent (TIP3P-MD) dynamics simulations will be presented. |
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Poster Session
6:00 PM-8:00 PM, Tuesday, August 21, 2007 BCEC -- Ballroom Foyer, Poster
Sci-Mix
Division of Computers in Chemistry |