Projector-Based Embedding Eliminates Density Functional Dependence for QM/MM Calculations of Reactions in Enzymes and Solution

Kara Elizabeth Ranaghan, Darya Shchepnovska, Simon Jonathan Bennie, Narin Lawan, Stephen Macrae, Jolanta Zurek, Frederick R Manby, Adrian J Mulholland*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

11 Citations (Scopus)
98 Downloads (Pure)

Abstract

Combined quantum mechanics/molecular mechanics (QM/MM) methods are increasingly widely utilized in studies of reactions in enzymes and other large systems. Here, we apply a range of QM/MM methods to investigate the Claisen rearrangement of chorismate to prephenate, in solution, and in the enzyme chorismate mutase. Using projector-based embedding in a QM/MM framework, we apply treatments up to the CCSD(T) level. We test a range of density functional QM/MM methods and QM region sizes. The results show that the calculated reaction energetics are significantly more sensitive to the choice of density functional than they are to the size of the QM region in these systems. Projector-based embedding of a wavefunction method in DFT reduced the 13 kcal/mol spread in barrier heights calculated at the DFT/MM level to a spread of just 0.3 kcal/mol, essentially eliminating dependence on the functional. Projector-based embedding of correlated ab initio methods provides a practical method for achieving high accuracy for energy profiles derived from DFT and DFT/MM calculations for reactions in condensed phases.

Original languageEnglish
Pages (from-to)2063-2078
Number of pages16
JournalJournal of Chemical Information and Modeling
Volume59
Issue number5
Early online date22 Feb 2019
DOIs
Publication statusPublished - 28 May 2019

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