Towards a cheminformatic design for quantum mechanical enzyme models: the case of catechol-O-methyltransferase

The efficiency, accuracy, and replicability of enzyme simulations is often hampered by ad hoc model design. To address this problem, we have developed the Residue Interaction Network ResidUe Selector (RINRUS) toolkit. RINRUS utilizes residue contact networks to automate construction of rational quantum mechanical cluster models. This work examines this problem by computing the reaction kinetics and thermodynamics for 508 models of the active site of catechol-o-methyltransferase, an enzyme which catalyzes the methyl transfer from S-adenosyl methionine cofactor to catechol substrates. Our results demonstrate using RINRUS to rationally design small and accurate active site models.