Density functional theory (DFT) is now extensively used as a research tool for the investigation of structure and reactivity of biological systems; however, its high computational demands still restrict the applicability of DFT to systems of a few tens up to one hundred atoms. A combined quantum mechanical/molecular mechanical (QM/MM) approach is applicable as an important method to study whole enzyme systems more than ten thousands atoms. We have investigated methane monooxygenase, dopamenie β-monooxygenase, tyrosinase, B12 dependent diol dehydratase, etc. using DFT and QM/MM calculations. In particular, we have done some computational mutation analyses about the amino acid residues at the active site of diol dehydratase. Our DFT and QM/MM calculations can correctly describe the structures and activation barriers of intermediates and transition states in the protein environment, and therefore, we successfully revealed the catalytic role of amino acid residues at the active site of diol dehydratase. Predicted relative activities of mutants are consistent with experimentally observed reaction rates. These results encourage us to apply QM/MM research to enzymatic reactions, functional analysis of active-site residues, and rational design of enzymes with new catalytic functions.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science