Novel 3D Descriptors Using Excluded Volume: Application to 3D Quantitative Structure−Activity Relationships
Yukio Tominaga, Iwao Fujiwara · Journal of Chemical Information and Computer Sciences · 1997
Comparative molecular field analysis (CoMFA) has been used in drug design and three-dimensional quantitative structure−activity relationships (3D-QSAR). The success of a CoMFA study depends on the quality of the alignment rule. In other words, the alignment rule is the key in CoMFA analysis, while it is not a simple task to determine the rule. We developed novel 3D descriptors, the van der Waals excluded volume of each molecule and probe, which do not require alignment rules and are not significantly affected by the orientation of the molecules. Each probe is constructed by the excluded volume of two spheres with different radii and the center identical to each molecule's center of gravity. We applied the descriptors to QSAR analysis of the data set for the binding of 21 steroids to corticosteroid-binding globulin (CBG) which was introduced by Dunne et al. and compared the result with that of CoMFA.