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Multiscale Chemical Modeling Using Quantum Mechanics/Molecular Mechanics (QM/MM) Methods: Advances and Applications

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Computational and Theoretical Chemistry".

Deadline for manuscript submissions: closed (28 February 2015) | Viewed by 47255

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Special Issue Editor

Prof. Dr. James Gauld

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Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada
Interests: computational chemistry; quantum mechanics/molecular mechanics; molecular dynamics; docking; catalysis; enzymology; thermochemistry; reaction mechanisms; sulfur biochemistry
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Dear Colleagues,

Hybrid quantum mechanics/molecular mechanics (QM/MM) methods marry the seemingly disparate quantum and molecular mechanical approaches. Their development has led to an explosion in the range and size of chemical problems that can be investigated computationally. For example, they allow one to use highly accurate QM methods to model the interactions and reactions within the active site of an enzyme, while simultaneously exploiting MM methods to model the rest of the protein. The impact of these methods across chemistry is difficult to overestimate and is further reinforced by the fact that recently, its three founding developers, Martin Karplus, Arieh Warshel, and Michael Levitt, were jointly awarded the 2013 Nobel Prize in Chemistry "for the development of multiscale models for complex chemical systems" [1]. This Special Issue of Molecules, "Multiscale Chemical Modeling Using Quantum Mechanics/Molecular Mechanics (QM/MM) Methods: Advances and Applications", highlights the tremendous impact such methods have had on the computational study of chemical phenomena, as well as their potential.

Dr. James W. Gauld
Guest Editor

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References

1. The Official Web Site of Nobel Prize. Available online: http://www.nobelprize.org/nobel_prizes/
chemistry/laureates/2013/press.html (accessed on 9 October 2013).

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Keywords

quantum mechanics
molecular mechanics
QM/MM
multiscale
chemical modeling
density functional theory

Published Papers (6 papers)

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Research

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2407 KiB

Open AccessArticle

Computational Study of Symmetric Methylation on Histone Arginine Catalyzed by Protein Arginine Methyltransferase PRMT5 through QM/MM MD and Free Energy Simulations

by Yufei Yue, Yuzhuo Chu and Hong Guo

Molecules 2015, 20(6), 10032-10046; https://doi.org/10.3390/molecules200610032 - 29 May 2015

Cited by 11 | Viewed by 7908

Abstract

Protein arginine methyltransferases (PRMTs) catalyze the transfer of the methyl group from S-adenosyl-l-methionine (AdoMet) to arginine residues. There are three types of PRMTs (I, II and III) that produce different methylation products, including asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and monomethylarginine (MMA). Since these different methylations can lead to different biological consequences, understanding the origin of product specificity of PRMTs is of considerable interest. In this article, the quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy simulations are performed to study SDMA catalyzed by the Type II PRMT5 on the basis of experimental observation that the dimethylated product is generated through a distributive fashion. The simulations have identified some important interactions and proton transfers during the catalysis. Similar to the cases involving Type I PRMTs, a conserved Glu residue (Glu435) in PRMT5 is suggested to function as general base catalyst based on the result of the simulations. Moreover, our results show that PRMT5 has an energetic preference for the first methylation on N_η1 followed by the second methylation on a different ω-guanidino nitrogen of arginine (N_η2).The first and second methyl transfers are estimated to have free energy barriers of 19–20 and 18–19 kcal/mol respectively. The computer simulations suggest a distinctive catalytic mechanism of symmetric dimethylation that seems to be different from asymmetric dimethylation. Full article

(This article belongs to the Special Issue Multiscale Chemical Modeling Using Quantum Mechanics/Molecular Mechanics (QM/MM) Methods: Advances and Applications)

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1016 KiB

Open AccessArticle

State-Dependent Molecular Dynamics

by Ciann-Dong Yang and Hung-Jen Weng

Molecules 2014, 19(10), 16122-16145; https://doi.org/10.3390/molecules191016122 - 09 Oct 2014

Cited by 1 | Viewed by 6164

Abstract

This paper proposes a new mixed quantum mechanics (QM)—molecular mechanics (MM) approach, where MM is replaced by quantum Hamilton mechanics (QHM), which inherits the modeling capability of MM, while preserving the state-dependent nature of QM. QHM, a single mechanics playing the roles of QM and MM simultaneously, will be employed here to derive the three-dimensional quantum dynamics of diatomic molecules. The resulting state-dependent molecular dynamics including vibration, rotation and spin are shown to completely agree with the QM description and well match the experimental vibration-rotation spectrum. QHM can be incorporated into the framework of a mixed quantum-classical Bohmian method to enable a trajectory interpretation of orbital-spin interaction and spin entanglement in molecular dynamics. Full article

(This article belongs to the Special Issue Multiscale Chemical Modeling Using Quantum Mechanics/Molecular Mechanics (QM/MM) Methods: Advances and Applications)

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2441 KiB

Open AccessArticle

A Multi-Scale Computational Study on the Mechanism of Streptococcus pneumoniae Nicotinamidase (SpNic)

by Bogdan F. Ion, Erum Kazim and James W. Gauld

Molecules 2014, 19(10), 15735-15753; https://doi.org/10.3390/molecules191015735 - 29 Sep 2014

Cited by 9 | Viewed by 7145

Abstract

Nicotinamidase (Nic) is a key zinc-dependent enzyme in NAD metabolism that catalyzes the hydrolysis of nicotinamide to give nicotinic acid. A multi-scale computational approach has been used to investigate the catalytic mechanism, substrate binding and roles of active site residues of Nic from Streptococcus pneumoniae (SpNic). In particular, density functional theory (DFT), molecular dynamics (MD) and ONIOM quantum mechanics/molecular mechanics (QM/MM) methods have been employed. The overall mechanism occurs in two stages: (i) formation of a thioester enzyme-intermediate (IC2) and (ii) hydrolysis of the thioester bond to give the products. The polar protein environment has a significant effect in stabilizing reaction intermediates and in particular transition states. As a result, both stages effectively occur in one step with Stage 1, formation of IC2, being rate limiting barrier with a cost of 53.5 kJ•mol⁻¹ with respect to the reactant complex, RC. The effects of dispersion interactions on the overall mechanism were also considered but were generally calculated to have less significant effects with the overall mechanism being unchanged. In addition, the active site lysyl (Lys103) is concluded to likely play a role in stabilizing the thiolate of Cys136 during the reaction. Full article

(This article belongs to the Special Issue Multiscale Chemical Modeling Using Quantum Mechanics/Molecular Mechanics (QM/MM) Methods: Advances and Applications)

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4310 KiB

Open AccessArticle

A Multi-Scale–Multi-Stable Model for the Rhodopsin Photocycle

by Francesco Tavanti and Valentina Tozzini

Molecules 2014, 19(9), 14961-14978; https://doi.org/10.3390/molecules190914961 - 18 Sep 2014

Cited by 11 | Viewed by 8842

Abstract

We report a multi-scale simulation study of the photocycle of the rhodopsins. The quasi-atomistic representation (“united atoms” UA) of retinal is combined with a minimalist coarse grained (CG, one-bead-per amino acid) representation of the protein, in a hybrid UA/CG approach, which is the homolog of QM/MM, but at lower resolution. An accurate multi-stable parameterization of the model allows simulating each state and transition among them, and the combination of different scale representation allows addressing the entire photocycle. We test the model on bacterial rhodopsin, for which more experimental data are available, and then also report results for mammalian rhodopsins. In particular, the analysis of simulations reveals the spontaneous appearance of meta-stable states in quantitative agreement with experimental data. Full article

(This article belongs to the Special Issue Multiscale Chemical Modeling Using Quantum Mechanics/Molecular Mechanics (QM/MM) Methods: Advances and Applications)

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640 KiB

Open AccessArticle

QM/MM Studies of Contemporary and Novel Membrane Raft Fluorescent Probes

by Hannah L. Blake and David Robinson

Molecules 2014, 19(7), 10230-10241; https://doi.org/10.3390/molecules190710230 - 15 Jul 2014

Cited by 4 | Viewed by 5511

Abstract

We have studied a number of contemporary and novel membrane probes, selected for their structural similarity to membrane raft components, in order to properly anchor themselves within a sphingolipid/cholesterol rich region. A QM/MM approach was adopted in order to understand the structural and electrostatic influences of fluorescence emission shifts of the probes in different lipid and solvation environments. The proposed modifications to the membrane probes have shown encouraging data relating not only to emission shifts within the membrane, but also their ability to anchor within a membrane raft domain and the stability to internalization within a membrane system. Full article

(This article belongs to the Special Issue Multiscale Chemical Modeling Using Quantum Mechanics/Molecular Mechanics (QM/MM) Methods: Advances and Applications)

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Review

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2130 KiB

Open AccessReview

QM/MM Calculations with deMon2k

by Dennis R. Salahub, Sergei Yu. Noskov, Bogdan Lev, Rui Zhang, Van Ngo, Annick Goursot, Patrizia Calaminici, Andreas M. Köster, Aurelio Alvarez-Ibarra, Daniel Mejía-Rodríguez, Jan Řezáč, Fabien Cailliez and Aurélien De la Lande

Molecules 2015, 20(3), 4780-4812; https://doi.org/10.3390/molecules20034780 - 16 Mar 2015

Cited by 19 | Viewed by 10503

Abstract

The density functional code deMon2k employs a fitted density throughout (Auxiliary Density Functional Theory), which offers a great speed advantage without sacrificing necessary accuracy. Powerful Quantum Mechanical/Molecular Mechanical (QM/MM) approaches are reviewed. Following an overview of the basic features of deMon2k that make it efficient while retaining accuracy, three QM/MM implementations are compared and contrasted. In the first, deMon2k is interfaced with the CHARMM MM code (CHARMM-deMon2k); in the second MM is coded directly within the deMon2k software; and in the third the Chemistry in Ruby (Cuby) wrapper is used to drive the calculations. Cuby is also used in the context of constrained-DFT/MM calculations. Each of these implementations is described briefly; pros and cons are discussed and a few recent applications are described briefly. Applications include solvated ions and biomolecules, polyglutamine peptides important in polyQ neurodegenerative diseases, copper monooxygenases and ultra-rapid electron transfer in cryptochromes. Full article

(This article belongs to the Special Issue Multiscale Chemical Modeling Using Quantum Mechanics/Molecular Mechanics (QM/MM) Methods: Advances and Applications)

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