Multistructural microiteration combined with QM/MM-ONIOM electrostatic embedding

Abstract

Multistructural microiteration (MSM) is a method to take account of contributions of multiple surrounding structures in a geometrical optimization or reaction path calculation using the quantum mechanics/molecular mechanics (QM/MM) ONIOM method. In this study, we combined MSM with the electrostatic embedding (EE) scheme of the QM/MM-ONIOM method by extending its original formulation for mechanical embedding (ME). MSM–EE takes account of the polarization in the QM region induced by point charges assigned to atoms in the multiple surrounding structures, where the point charges are scaled by the weight factor of each surrounding structure determined through MSM. The performance of MSM–EE was compared with that of the other methods, i.e., ONIOM–ME, ONIOM–EE, and MSM–ME, by applying them to three chemical processes: (1) chorismate-to-prephenate transformation in aqueous solution, (2) the same transformation as (1) in an enzyme, and (3) hydroxylation in p-hydroxybenzoate hydroxylase. These numerical tests of MSM–EE yielded barriers and reaction energies close to experimental values with computational costs comparable to those of the other three methods.