QSAR modeling of human catechol O -methyltransferase enzyme kinetics

摘要

QSAR models based on two different similarity methods were developed to predict two enzyme kinetic parameters K _m, and V _max for catecholic substrates of human soluble catechol O-methyl-transferase (S-COMT). The similarity of the data set is measured using: (a) the 3D molecular structure, by TOPOCLUJ software, and (b) classical topological descriptors, by SIMIL program. The measured properties of 45 substrates were correlated with the topological and electronic parameters of the graphs associated to molecular structures. Clustering methods based on similarity descriptors succeeded a better prediction than the method using 3D structure similarity. All models were statistically significant and showed good stability to data variation in leave-one-out (LOO) cross-validation experiment.