QM/MM Molecular Dynamics Studies of Metal Binding Proteins
Vidossich, Pietro (Universitat Autònoma de Barcelona. Departament de Química)
Magistrato, Alessandra (CNR-IOM-Democritos National Simulation Center)

Date:	2014
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Car-Parrinello molecular dynamics ; QM/MM simulations ; Enzymatic catalysis ; Peroxidases ; Ribozymes ; Beta-lactamases ; Alpha-synuclein ; Transition metals
Published in:	Biomolecules, Vol. 4 (july 2014) , p. 616-645, ISSN 2218-273X

DOI: 10.3390/biom4030616
PMID: 25006697

30 p, 1.5 MB

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