Quantum mechanical (QM) cluster approach is a useful and convenient tool to study mechanisms of enzymatic reactions. Our investigation is to propose a proper QM-cluster that reproduces the special specificity of glyoxalase I (GlxI). GlxI converts S and R enantiomers of hemithioacetal to only S-D enantiomer of its product. It shows this special specificity with two glutamate residues that are symmetrically coordinated to a Zn ion. However, molecular dynamics simulations showed that one of the glutamates, Glu-172 is more flexible than the other one, Glu-99. Results indicate a QMcluster with a more flexible model of Glu-172, can reproduce proposed mechanisms for the Ssubstrate. However, the same cluster can reach the R-L enantiomer of the product from the R substrate. We propose the necessity of using much more expensive, hybrid QM/MM methods or a very big QM-cluster to model and study reaction mechanisms of stereospecific enzymes like GlxI.
