On the Stability of CoMFA Models

Abstract
Abrupt, smooth, and box methods for the calculation of electrostatic and steric field values in the comparative molecular field analysis (CoMFA) 3D QSAR technique are assessed on three diverse data sets of medicinal chemistry interest. While the standard CoMFA settings are robust to small changes in the position of the lattice, superior results may sometimes be obtained by use of only one field. However, if only the electrostatic field is used, then sometimes large differences between models are apparent. This appears to be due to a lack of column dropping, and these difficulties can be remedied by use of the box method.