Use of 3D QSAR Models for Database Screening: A Feasibility Study

The applicability and scope of 3D QSAR methods (CoMFA, CoMSIA) to screen databases are examined.
A protocol requiring minimal user intervention has been established to align training and test set molecules
using FlexS. As model system isozymes of human carbonic anhydrase (hCA) are used, all results are
exemplified studying affinity toward hCA II and selectivity between hCA I and II. The predictive power of
the obtained models is assessed through prediction of 663 compounds not included in the training set and
compared to 2D QSAR models derived from fragment (MACCS) or property (VSA) based descriptors. The
predictive power is evaluated with respect to the following criteria:  the numerical, concerning the absolute
accuracy of prediction, and the categorical, characterizing the ability to assign a compound to the correct
activity class.