title: Quantum Mechanics/Molecular Mechanics Modeling of Enzymatic Processes: Caveats and Breakthroughs.
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.
authors.affiliation: Jerzy Haber Institute of Catalysis and Surface Chemistry of the, Polish Academy of Sciences, Niezapominajek 8, 30-239, Krakow, Poland. mgquesne@gmail.com.|Manchester Institute of Biotechnology and, School of Chemical Engineering and Analytical Science, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK. mgquesne@gmail.com.
authors.forename: Matthew G
authors.identifier: http://orcid.org/0000-0001-5130-1266
authors.initials: MG
authors.lastname: Quesne
authors.affiliation: Jerzy Haber Institute of Catalysis and Surface Chemistry of the, Polish Academy of Sciences, Niezapominajek 8, 30-239, Krakow, Poland. ncborows@cyf-kr.edu.pl.
authors.forename: Tomasz
authors.identifier: http://orcid.org/0000-0002-3450-3576
authors.initials: T
authors.lastname: Borowski
authors.affiliation: Manchester Institute of Biotechnology and, School of Chemical Engineering and Analytical Science, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK. sam.devisser@manchester.ac.uk.
authors.forename: Sam P
authors.identifier: http://orcid.org/0000-0002-2620-8788
authors.initials: SP
authors.lastname: de Visser
keywords: QM/MM; computational modeling; density functional theory; enzyme catalysis; enzyme mechanisms