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Front. Chem. | doi: 10.3389/fchem.2018.00089

On the difference between additive and subtractive QM/MM calculations

Lili Cao1 and  Ulf Ryde1*
  • 1Theoretical Chemistry, Lund University, Sweden

The combined quantum mechanical (QM) and molecular mechanical (MM) approach (QM/MM) is a popular method to study reactions in biochemical macromolecules. Even if the general procedure of using QM for a small, but interesting part of the system and MM for the rest is common to all approaches, the details of the implementations vary extensively, especially the treatment of the interface between the two systems. For example, QM/MM can use either additive or subtractive schemes, of which the former is often said to be preferable, although the two schemes are often mixed up with mechanical and electrostatic embedding. In this article, we clarify the similarities and differences of the two approaches. We show that inherently, the two approaches should be identical and in practice require the same sets of parameters. However, the subtractive scheme provides an opportunity to correct errors introduced by the truncation of the QM system, i.e. the link atoms, but such corrections require additional MM parameters for the QM system. We describe and test three types of link-atom correction, viz. for van der Waals, electrostatic and bonded interactions. The calculations show that electrostatic and bonded link-atom corrections often give rise to problems in the geometries and energies. The van der Waals link-atom corrections are quite small and give results similar to a pure additive QM/MM scheme. Therefore, both approaches can be recommended.

Keywords: QM/MM, Haem oxygenase, Sulfite Oxidase, Mechanical embedding, Electrostatic embedding, additive QM/MM, subtractive QM/MM.

Received: 31 Jan 2018; Accepted: 14 Mar 2018.

Edited by:

Sam P. De Visser, University of Manchester, United Kingdom

Reviewed by:

Albert Poater, University of Girona, Spain
Jiayun Pang, University of Greenwich, United Kingdom  

Copyright: © 2018 Cao and Ryde. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Ulf Ryde, Lund University, Theoretical Chemistry, Chemical Centre, P. O. Box 124, Lund, 221 00, Sweden,