Article ID Journal Published Year Pages File Type
443708 Journal of Molecular Graphics and Modelling 2007 14 Pages PDF
Abstract

Molecular dynamics (MD) simulations were carried out for inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) isoforms complexed with substrate (l-arginine) and the iNOS specific inhibitor GW 273629, 2 for a time period of 1.2 ns. The simulations were compared both within and across the isoforms. iNOS specificity of inhibitor 2 is attributed to water mediated interactions and cooperative hydrogen bond networks. Juxtaposition of the carboxylic and ammonium groups in the substrate and inhibitor serve as a modulating key in binding to the isoforms. Based on these investigations, molecules 3 and 4 were rationally designed to attain specificity among the isoforms. The capability of the designed ligands was theoretically tested through MD simulations to envisage binding patterns with both isoforms. A detailed analysis of the molecular recognition pattern shows molecule 4 to be more selective to iNOS when compared to eNOS.

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Physical Sciences and Engineering Chemistry Physical and Theoretical Chemistry
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