Conformational effects in enzyme catalysis: QM/MM free energy calculation of the ‘NAC’ contribution in chorismate mutase

Abstract

The controversial ‘near attack conformation’ (NAC) effect in the important model enzyme chorismate mutase is calculated to be 3.8–4.6 kcal mol⁻¹ by QM/MM free energy perturbation molecular dynamics methods, showing that the NAC effect by itself does not account for catalysis in this enzyme.