Chemical Function Based Alignment Generation for 3D QSAR of Highly Flexible Platelet Aggregation Inhibitors

Abstract

It is well established that the quality of 3D QSAR experiments relies on one or multiple consistent 3D alignments for an ensemble of molecules as starting point for the calculations, especially when these molecules present a high degree of flexibility. Among the different phannacophore identification techniques, the feature-based alignment methodology constitutes a useful approach [1]. To illustrate this methodology, we used a training set of 24 platelet aggregation inhibitors [2] (thromboxane A₂ receptor antagonists, TXRA / thromboxane synthetase inhibitors, TXSI) with affinities covering a range over four orders of magnitude for the receptor and two orders of magnitude for the enzyme.