Influence of the Conditions in Pharmacophore Generation,Scoring,and 3D Database Search for Chemical Feature-Based Pharmacophore Models:One Application Study of ET_A-and ET_B-Selective Antagonists

摘要

Using the commercial pharmacophore modeling suite Catalyst,we have studied the influence of the compare.scaledMultiBlobFeatureErrors .Catalyst parameter.The influence of this parameter has been studied in pharmacophore generation,hypothesis scoring,and database searching.This parameter,introduced in Catalyst 4.7,changed its default value in Catalyst 4.8,and it strongly influences the statistical quality of pharmacophore generation,scoring of the hypotheses,and database searching.Two different pharmacophore models have been constructed for the ET_A and ET_B receptor antagonists.Both models contain one positive ionizable,one negative ionizable,one hydrogen-bond acceptor,one hydrophobic aromatic,and one hydrophobic aliphatic feature.The models have been compared,and some differences in the position of the hydrogen-bond acceptor in the putative binding pocket have been highlighted.