Modeling enzymatic processes: A molecular simulation analysis of the origins of regioselectivity

Enzymes hold a great synthetic importance as catalysts for the selective transformation of compounds. We have investigated the origins of the regioselectivity difference in the subtilisin mediated acylation of d- and l-benzylglucopiranoside compounds. Using molecular dynamics and QM/MM calculations we have investigated the molecular recognition of the substrates by the enzyme active site and the differences in energy of the tetrahedral intermediates (TI) mimicking the acylation transition states leading to different selectivities. QM/MM analysis of the energy–structure correlations of the TIs shows a clustering towards lower energy of the conformations corresponding to the major experimental products for each enantiomer.