Volume 22, Issue 8 p. 2562-2581
Review

Quantum Mechanics/Molecular Mechanics Modeling of Enzymatic Processes: Caveats and Breakthroughs

Dr. Matthew G. Quesne

Corresponding Author

Dr. Matthew G. Quesne

Jerzy Haber Institute of Catalysis and Surface Chemistry of the, Polish Academy of Sciences, Niezapominajek 8, 30-239 Krakow, Poland

Manchester Institute of Biotechnology and, School of Chemical Engineering and Analytical Science, The University of Manchester, 131 Princess Street, Manchester, M1 7DN UK

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Dr. Tomasz Borowski

Corresponding Author

Dr. Tomasz Borowski

Jerzy Haber Institute of Catalysis and Surface Chemistry of the, Polish Academy of Sciences, Niezapominajek 8, 30-239 Krakow, Poland

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Dr. Sam P. de Visser

Corresponding Author

Dr. Sam P. de Visser

Manchester Institute of Biotechnology and, School of Chemical Engineering and Analytical Science, The University of Manchester, 131 Princess Street, Manchester, M1 7DN UK

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First published: 23 December 2015
Citations: 127

Graphical Abstract

The do′s and don'ts of QM/MM: This manuscript gives a tutorial review on the challenges and caveats of running QM/MM calculations and explains the reader the key steps in the set-up processes.

Abstract

Nature has developed large groups of enzymatic catalysts with the aim to transfer substrates into useful products, which enables biosystems to perform all their natural functions. As such, all biochemical processes in our body (we drink, we eat, we breath, we sleep, etc.) are governed by enzymes. One of the problems associated with research on biocatalysts is that they react so fast that details of their reaction mechanisms cannot be obtained with experimental work. In recent years, major advances in computational hardware and software have been made and now large (bio)chemical systems can be studied using accurate computational techniques. One such technique is the quantum mechanics/molecular mechanics (QM/MM) technique, which has gained major momentum in recent years. Unfortunately, it is not a black-box method that is easily applied, but requires careful set-up procedures. In this work we give an overview on the technical difficulties and caveats of QM/MM and discuss work-protocols developed in our groups for running successful QM/MM calculations.