MULTIWAY CALIBRATION IN 3D QSAR

We have introduced multilinear PLS in 3D QSAR and applied it to GRID d escriptors from a set of benzamides with affinity to the dopamine D-3 receptor subtype, synthesized as potential drugs against schizophrenia . The key issue in 3D QSAR modelling is to obtain a predictive model t hat is easy to interpret, Each component in the multilinear PLS model explains clearly defined details, e.g. substituent positions, while th e bilinear PLS solution is general and more difficult to interpret. Th e best models were obtained after four components with multilinear PLS (Q(2) = 51%) and after only one component with bilinear PLS (Q(2) = 5 0%). The external test set was predicted better with multilinear PLS ( Q(2) = 31%) than with bilinear PLS (Q(2) = 25%). With multilinear PLS one loses in fit and gains in stability and simplicity owing to the fe wer parameters that need to be estimated as compared with bilinear PLS . Finally, multilinear PLS is also less influenced by insignificant va riation in the descriptor block, which is an advantage in 3D QSAR mode lling. (C) 1997 John Wiley & Sons, Ltd.