A molecular dynamics study of the stability of chymotrypsin acyl enzymes

We have investigated the enantioselectivity observed in the deacylation rates of a beta -substituted beta -substituted beta -phenylpropionyl chymotrypsin acyl enzyme by molecular dynamics simulations. The results provide a rationalization for the deacylation enantioselectivity of these acyl enzymes: the reduced deacylation rate of the R enantiomer could arise from less effective hydrogen-bonding stabilization of both the ester carbonyl in the acyl enzyme and the oxyanion in the deacylation tetrahedral intermediate by the oxyanion binding hole site; the S enantiomer, which preserves excellent hydrogen bond distances and geometry at both stages, is more ideally set up for the attack of water that leads to deacylation.