کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
443708 | 692756 | 2007 | 14 صفحه PDF | دانلود رایگان |

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.
Journal: Journal of Molecular Graphics and Modelling - Volume 26, Issue 2, September 2007, Pages 457–470