Combined Use of Factorial Design and Comparative Molecular Field Analysis (CoMFA): a Case Study.

The factorial design (FD) strategy has been applied within the CoMFA framework to a set of 71 N-acyl-L-aminoacid esters undergoing hydrolysis by alpha-chymotripsin. The steric and electrostatic fields of the molecules aligned in their enzyme-bound conformations have been subjected to Principle Component Analysis (PCA) and three latent variables have been extracted to build up an FD scheme. Two different training sets of 12 compounds have been formed which satisfy the FD criteria. In addition to these two rationally designed series, 50 training sets of 12 structures have been defined through a random selection procedure.