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. (c) 2005 Elsevier B.V. All
rights reserved.