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Advances in Modeling of Chemical Reactions by QM/MM Calculations

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

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 11644

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Special Issue Editor

Dr. Demeter Tzeli

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Guest Editor

Laboratory of Physical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 157 84 Zografou, Greece
Interests: computational and theoretical chemistry; ab initio calculations; DFT calculations; encapsulation; molecular logic gates; molecular sensors; photoinduced charge transfer processes; supramolecular systems; bonding analysis
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Special Issue Information

Dear Colleagues,

In the last several decades, the hybrid methodology, quantum mechanics/molecular mechanics (QM/MM), has become one of the most used techniques to model molecules embedded in a complex environment. Currently, it is the state-of-the-art for computational studies of chemical reactions and electronic properties in biomolecular systems. Chemical reactions are ubiquitous in biology, controlling a wide variety of fundamental biological processes, such as photosynthesis, bioluminescence, etc. It is crucial to obtain a full understanding of chemical mechanisms, and to confirm or discard different mechanistic proposals when they cannot be elucidated from experimental data.

To date, QM/MM methods have been applied to gain insight into different issues, such as enzymatic reaction mechanisms, the calculation of transition state structures, intermediates, activation energies, spectroscopic properties, electronically excited states, pKa values, etc. The multiple strengths of QM/MM methods are that they balance the simulation cost and accuracy, and the fact that large molecules can be modelled explicitly including the entire studied system in the calculations. In contrast, the main limitation of QM/MM calculations is that there are many possible conformations that macromolecules can assume. However, the available crystallographic structures can substantially aid in the modeling setup and preparation.

This Issue aims to gather new ideas and methodologies on all aspects of QM/MM techniques, as well as research studies on biomolecular or complex systems. Contributions in the form of both original research and review articles are particularly welcome.

Prof. Demeter Tzeli
Guest Editor

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind 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 semimonthly 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 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

quantum mechanics/molecular mechanics (QM/MM)
modeling
biomolecular systems
reaction mechanisms
calculations

Published Papers (3 papers)

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Research

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15 pages, 5276 KiB

Open AccessArticle

Mechanism of Guanosine Triphosphate Hydrolysis by the Visual Proteins Arl3-RP2: Free Energy Reaction Profiles Computed with Ab Initio Type QM/MM Potentials

by Maria G. Khrenova, Egor S. Bulavko, Fedor D. Mulashkin and Alexander V. Nemukhin

Molecules 2021, 26(13), 3998; https://doi.org/10.3390/molecules26133998 - 30 Jun 2021

Cited by 6 | Viewed by 2263

Abstract

We report the results of calculations of the Gibbs energy profiles of the guanosine triphosphate (GTP) hydrolysis by the Arl3-RP2 protein complex using molecular dynamics (MD) simulations with ab initio type QM/MM potentials. The chemical reaction of GTP hydrolysis to guanosine diphosphate (GDP) and inorganic phosphate (Pi) is catalyzed by GTPases, the enzymes, which are responsible for signal transduction in live cells. A small GTPase Arl3, catalyzing the GTP → GDP reaction in complex with the activating protein RP2, constitute an essential part of the human vision cycle. To simulate the reaction mechanism, a model system is constructed by motifs of the crystal structure of the Arl3-RP2 complexed with a substrate analog. After selection of reaction coordinates, energy profiles for elementary steps along the reaction pathway GTP + H₂O → GDP + Pi are computed using the umbrella sampling and umbrella integration procedures. QM/MM MD calculations are carried out, interfacing the molecular dynamics program NAMD and the quantum chemistry program TeraChem. Ab initio type QM(DFT)/MM potentials are computed with atom-centered basis sets 6-31G** and two hybrid functionals (PBE0-D3 and ωB97x-D3) of the density functional theory, describing a large QM subsystem. Results of these simulations of the reaction mechanism are compared to those obtained with QM/MM calculations on the potential energy surface using a similar description of the QM part. We find that both approaches, QM/MM and QM/MM MD, support the mechanism of GTP hydrolysis by GTPases, according to which the catalytic glutamine side chain (Gln71, in this system) actively participates in the reaction. Both approaches distinguish two parts of the reaction: the cleavage of the phosphorus-oxygen bond in GTP coupled with the formation of Pi, and the enzyme regeneration. Newly performed QM/MM MD simulations confirmed the profile predicted in the QM/MM minimum energy calculations, called here the pathway-I, and corrected its relief at the first elementary step from the enzyme–substrate complex. The QM/MM MD simulations also revealed another mechanism at the part of enzyme regeneration leading to pathway-II. Pathway-II is more consistent with the experimental kinetic data of the wild-type complex Arl3-RP2, whereas pathway-I explains the role of the mutation Glu138Gly in RP2 slowing down the hydrolysis rate. Full article

(This article belongs to the Special Issue Advances in Modeling of Chemical Reactions by QM/MM Calculations)

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15 pages, 3528 KiB

Open AccessArticle

Simulating Absorption Spectra of Flavonoids in Aqueous Solution: A Polarizable QM/MM Study

by Sulejman Skoko, Matteo Ambrosetti, Tommaso Giovannini and Chiara Cappelli

Molecules 2020, 25(24), 5853; https://doi.org/10.3390/molecules25245853 - 11 Dec 2020

Cited by 15 | Viewed by 3715

Abstract

We present a detailed computational study of the UV/Vis spectra of four relevant flavonoids in aqueous solution, namely luteolin, kaempferol, quercetin, and myricetin. The absorption spectra are simulated by exploiting a fully polarizable quantum mechanical (QM)/molecular mechanics (MM) model, based on the fluctuating charge (FQ) force field. Such a model is coupled with configurational sampling obtained by performing classical molecular dynamics (MD) simulations. The calculated QM/FQ spectra are compared with the experiments. We show that an accurate reproduction of the UV/Vis spectra of the selected flavonoids can be obtained by appropriately taking into account the role of configurational sampling, polarization, and hydrogen bonding interactions. Full article

(This article belongs to the Special Issue Advances in Modeling of Chemical Reactions by QM/MM Calculations)

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Review

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28 pages, 1874 KiB

Open AccessReview

Review on the QM/MM Methodologies and Their Application to Metalloproteins

by Christina Eleftheria Tzeliou, Markella Aliki Mermigki and Demeter Tzeli

Molecules 2022, 27(9), 2660; https://doi.org/10.3390/molecules27092660 - 20 Apr 2022

Cited by 31 | Viewed by 4887

Abstract

The multiscaling quantum mechanics/molecular mechanics (QM/MM) approach was introduced in 1976, while the extensive acceptance of this methodology started in the 1990s. The combination of QM/MM approach with molecular dynamics (MD) simulation, otherwise known as the QM/MM/MD approach, is a powerful and promising tool for the investigation of chemical reactions’ mechanism of complex molecular systems, drug delivery, properties of molecular devices, organic electronics, etc. In the present review, the main methodologies in the multiscaling approaches, i.e., density functional theory (DFT), semiempirical methodologies (SE), MD simulations, MM, and their new advances are discussed in short. Then, a review on calculations and reactions on metalloproteins is presented, where particular attention is given to nitrogenase that catalyzes the conversion of atmospheric nitrogen molecules N₂ into NH₃ through the process known as nitrogen fixation and the FeMo-cofactor. Full article

(This article belongs to the Special Issue Advances in Modeling of Chemical Reactions by QM/MM Calculations)

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