Three-dimensional quantitative structure-activity relationship analyses using comparative molecular field analysis and comparative molecular similarity indices analysis to elucidate selectivity differences of inhibitors binding to trypsin, thrombin, and factor Xa.

摘要: Three-dimensional quantitative structure−activity relationship (3D QSAR) methods were applied using a training set of 72 inhibitors the benzamidine type with respect to their binding affinities (Ki values) toward thrombin, trypsin, and factor Xa yield statistically reliable models good predictive power. Two compared:  widely used comparative molecular field analysis (CoMFA) recently reported CoMSIA approach (comparative similarity indices analysis). produced significantly better results for all correlations. Furthermore, in contrast CoMFA, is not sensitive changes orientation superimposed molecules lattice. The correlation obtained by graphically interpreted terms contribution maps allowing physicochemical properties relevant be easily mapped back onto structures. advantage this feature demonstrated design new molecules. Finally, m...