Multivariate Free-Wilson analysis of α-chymotrypsin inhibitors using PLS

PLS modelling of the inhibitory activity of carboxylic esters in α-chymotrypsin based on Free-Wilson descriptors was described. The resulting PLS model was robust and predictive for designing new potent inhibitors of α-chymotrypsin. D-optimal designs were used for selecting the training and test set for external validation of the PLS model. The contributions of structural fragments to the inhibitory activity were examined by the MLR-like model transformed from the PLS model. Finally, the best candidate compound using the PLS model was synthesized and its inhibitory activity was evaluated.