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Biomolecules 2014, 4(3), 616-645; doi:10.3390/biom4030616

QM/MM Molecular Dynamics Studies of Metal Binding Proteins

1
Department of Chemistry, Autonomous University of Barcelona, 08193 Cerdanyola del Vallés, Spain
2
German Research School for Simulation Sciences, D-52425 Jülich, Germany
3
CNR-IOM-Democritos National Simulation Center c/o, International School for Advanced Studies (SISSA/ISAS), via Bonomea 265, 34165 Trieste, Italy
*
Author to whom correspondence should be addressed.
Received: 18 March 2014 / Revised: 5 June 2014 / Accepted: 6 June 2014 / Published: 8 July 2014
(This article belongs to the Special Issue Metal Binding Proteins)
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Abstract

Mixed quantum-classical (quantum mechanical/molecular mechanical (QM/MM)) simulations have strongly contributed to providing insights into the understanding of several structural and mechanistic aspects of biological molecules. They played a particularly important role in metal binding proteins, where the electronic effects of transition metals have to be explicitly taken into account for the correct representation of the underlying biochemical process. In this review, after a brief description of the basic concepts of the QM/MM method, we provide an overview of its capabilities using selected examples taken from our work. Specifically, we will focus on heme peroxidases, metallo-β-lactamases, α-synuclein and ligase ribozymes to show how this approach is capable of describing the catalytic and/or structural role played by transition (Fe, Zn or Cu) and main group (Mg) metals. Applications will reveal how metal ions influence the formation and reduction of high redox intermediates in catalytic cycles and enhance drug metabolism, amyloidogenic aggregate formation and nucleic acid synthesis. In turn, it will become manifest that the protein frame directs and modulates the properties and reactivity of the metal ions. View Full-Text
Keywords: Car–Parrinello molecular dynamics; QM/MM simulations; enzymatic catalysis; peroxidases; ribozymes; beta-lactamases; alpha-synuclein; transition metals Car–Parrinello molecular dynamics; QM/MM simulations; enzymatic catalysis; peroxidases; ribozymes; beta-lactamases; alpha-synuclein; transition metals
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Vidossich, P.; Magistrato, A. QM/MM Molecular Dynamics Studies of Metal Binding Proteins. Biomolecules 2014, 4, 616-645.

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