Chemical accuracy in QM/MM calculations on enzyme-catalysed reactions

Abstract

Combined quantum mechanics/molecular mechanics (QM/MM) modelling has the potential to answer fundamental questions about enzyme mechanisms and catalysis. Calculations using QM/MM methods can now predict barriers for enzyme-catalysed reactions with unprecedented, near chemical accuracy, i.e. to within I kcal/mol in the best cases. Quantitative predictions from firstprinciples calculations were only previously possible for very small molecules. At this level, quantitative, reliable predictions can be made about the mechanisms of enzyme-catalysed reactions. This development signals a new era of computational biochemistry.