E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

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

Quicklinks

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

Deadline for manuscript submissions: closed (28 February 2015)

Special Issue Editor

Guest Editor
Dr. James W. Gauld (Website)

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

Special Issue Information

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

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).


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).

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).

Keywords

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

Published Papers (6 papers)

View options order results:
result details:
Displaying articles 1-6
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Computational Study of Symmetric Methylation on Histone Arginine Catalyzed by Protein Arginine Methyltransferase PRMT5 through QM/MM MD and Free Energy Simulations
Molecules 2015, 20(6), 10032-10046; doi:10.3390/molecules200610032
Received: 3 March 2015 / Revised: 18 May 2015 / Accepted: 25 May 2015 / Published: 29 May 2015
Cited by 3 | PDF Full-text (2407 KB) | HTML Full-text | XML Full-text
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 [...] Read more.
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 Nη1 followed by the second methylation on a different ω-guanidino nitrogen of arginine (Nη2).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
Open AccessArticle State-Dependent Molecular Dynamics
Molecules 2014, 19(10), 16122-16145; doi:10.3390/molecules191016122
Received: 24 July 2014 / Revised: 4 September 2014 / Accepted: 17 September 2014 / Published: 9 October 2014
PDF Full-text (1016 KB) | HTML Full-text | XML Full-text
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 [...] Read more.
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
Open AccessArticle A Multi-Scale Computational Study on the Mechanism of Streptococcus pneumoniae Nicotinamidase (SpNic)
Molecules 2014, 19(10), 15735-15753; doi:10.3390/molecules191015735
Received: 28 August 2014 / Revised: 20 September 2014 / Accepted: 22 September 2014 / Published: 29 September 2014
Cited by 2 | PDF Full-text (2441 KB) | HTML Full-text | XML Full-text | Supplementary Files
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 [...] Read more.
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
Figures

Open AccessArticle A Multi-Scale–Multi-Stable Model for the Rhodopsin Photocycle
Molecules 2014, 19(9), 14961-14978; doi:10.3390/molecules190914961
Received: 21 July 2014 / Revised: 28 August 2014 / Accepted: 8 September 2014 / Published: 18 September 2014
Cited by 3 | PDF Full-text (4310 KB) | HTML Full-text | XML Full-text | Supplementary Files
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 [...] Read more.
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
Figures

Open AccessArticle QM/MM Studies of Contemporary and Novel Membrane Raft Fluorescent Probes
Molecules 2014, 19(7), 10230-10241; doi:10.3390/molecules190710230
Received: 16 June 2014 / Revised: 9 July 2014 / Accepted: 10 July 2014 / Published: 15 July 2014
Cited by 1 | PDF Full-text (640 KB) | HTML Full-text | XML Full-text
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 [...] Read more.
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

Review

Jump to: Research

Open AccessReview QM/MM Calculations with deMon2k
Molecules 2015, 20(3), 4780-4812; doi:10.3390/molecules20034780
Received: 19 September 2014 / Revised: 25 February 2015 / Accepted: 2 March 2015 / Published: 16 March 2015
Cited by 3 | PDF Full-text (2130 KB) | HTML Full-text | XML Full-text
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 [...] Read more.
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

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type: Review
Title: "The Challenge of Assigning Molecular Graphs Along the Potential Energy Surface of an Enzyme-Catalyzed Reaction"
Authors: Jorge Llano 1,* and James W. Gauld 2
Affiliations: 1 Department of Physical Sciences, MacEwan University, PO Box 1796, Edmonton, Alberta T5J 2P2, Canada;
2 Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B 3P4, Canada; E-
Abstract: The potential energy surface (PES) of an enzyme-catalyzed reaction can be computed by the effective combination of quantum mechanical (QM) methods, which describe the active site with bound substrate, and  molecular mechanical (MM) methods, which incorporate the anisotropic electrostatic and steric effects of the protein's tertiary structure on the active-site complex. The reaction coordinate in the PES consists of a collection of Cartesian coordinates of nuclei in the three dimensional space. A molecular graph allows us to draw a stereochemical representation of localized electron domains on a nuclei framework corresponding to a point of the PES. The assignment of a molecular graph to a nuclei framework is done qualitatively or quantitatively. A qualitative assignment is usually achieved by educated guesses drawn from typical interatomic distances, atomic charges and spin densities. In this review, we discuss how such assignments are achieved quantitatively in the realms of valence-bond theory and of molecular orbital theory through natural bond orbital (NBO) and atoms-in-molecules (AIM) analyses.

Journal Contact

MDPI AG
Molecules Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
molecules@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Molecules
Back to Top