Connecting traditional QSAR and molecular simulations of papain hydrolysis: importance of charge transfer

Abstract Molecular dynamics and full structure LocalSCF semi-empirical quantum mechanics calculations of receptor–ligand complexes were carried out to investigate structure–activity relationship for the papain hydrolysis of a series of N -benzoylglycine esters and reinterpret traditional QSAR descriptors using detailed structural information. A correlation of r 2  = 0.694 was obtained and it was shown that the pattern of charge distribution on the ester group is different if charges of free or complex ligands or are analyzed. The results can help to understand how traditional QSAR descriptors, such as F or σ , interacts with other electronic effects during complex formation.