<scp>TeraChem</scp>: A graphical processing unit<scp>‐accelerated</scp> electronic structure package for <scp>large‐scale</scp> ab initio molecular dynamics

Seritan, Stefan; Bannwarth, Christoph; Fales, B. Scott; Hohenstein, Edward G.; Isborn, Christine M.; Schumacher, Sara I. L. Kokkila; Li, Xin; Liu, Fang; Luehr, Nathan; Snyder, James W.; Song, Changjiang; Titov, Alexey V.; Ufimtsev, Ivan S.; Wang, Lee‐Ping; Martı́nez, Todd J.

doi:10.1002/wcms.1494

Cited by 213 publications

(195 citation statements)

References 143 publications

(168 reference statements)

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“…The NAMD [ 51 ] program was utilized for MD steps performance and calculation of forces and energies of the MM subsystem. The TeraChem program [ 57 ] was used to calculate forces in the QM region, and a NAMD-TeraChem interface [ 58 ] was applied. The cutoff distance on the point charges of the MM subsystem contributing to the QM Hamiltonian was 12 Å. Gibbs energy profiles of the OH − nucleophilic attack were calculated using the umbrella sampling approach.…”

Section: Models and Methodsmentioning

confidence: 99%

Boronic Acids as Prospective Inhibitors of Metallo-β-Lactamases: Efficient Chemical Reaction in the Enzymatic Active Site Revealed by Molecular Modeling

Krivitskaya

Khrenova

2021

Molecules

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Boronic acids are prospective compounds in inhibition of metallo-β-lactamases as they form covalent adducts with the catalytic hydroxide anion in the enzymatic active site upon binding. We compare this chemical reaction in the active site of the New Delhi metallo-β-lactamase (NDM-1) with the hydrolysis of the antibacterial drug imipenem. The nucleophilic attack occurs with the energy barrier of 14 kcal/mol for imipenem and simultaneously upon binding a boronic acid inhibitor. A boron atom of an inhibitor exhibits stronger electrophilic properties than the carbonyl carbon atom of imipenem in a solution that is quantified by atomic Fukui indices. Upon forming the prereaction complex between NDM-1 and inhibitor, the lone electron pair of the nucleophile interacts with the vacant p-orbital of boron that facilitates the chemical reaction. We analyze a set of boronic acid compounds with the benzo[b]thiophene core complexed with the NDM-1 and propose quantitative structure-sroperty relationship (QSPR) equations that can predict IC50 values from the calculated descriptors of electron density. These relations are applied to classify other boronic acids with the same core found in the database of chemical compounds, PubChem, and proposed ourselves. We demonstrate that the IC50 values for all considered benzo[b]thiophene-containing boronic acid inhibitors are 30–70 μM.

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Section: Models and Methodsmentioning

confidence: 99%

Boronic Acids as Prospective Inhibitors of Metallo-β-Lactamases: Efficient Chemical Reaction in the Enzymatic Active Site Revealed by Molecular Modeling

Krivitskaya

Khrenova

2021

Molecules

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“…In this respect, in 2017 GFN1‐xTB filled a gap in the market of off‐the‐shelf atomistic models as it is fast, robust, reasonably accurate, and works for many metallic systems. It was quickly adapted by the community and implemented in various QC programs like AMS, 18 CP2K, 19 Cuby4, 20 DFTB+, 21 entos, 22 ORCA, 23,24 and TeraChem 25,26 …”

Section: Introductionmentioning

confidence: 99%

Extended tight‐binding quantum chemistry methods

Bannwarth

Caldeweyher

Ehlert

et al. 2020

WIREs Comput Mol Sci

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967

964

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This review covers a family of atomistic, mostly quantum chemistry (QC) based semiempirical methods for the fast and reasonably accurate description of large molecules in gas and condensed phase. The theory is derived from a density functional (DFT) perturbation expansion of the electron density in fluctuation terms to various orders similar to the original density functional tight binding model. The term “eXtended” in their name (xTB) emphasizes the parameter availability for almost the entire periodic table of elements (Z ≤ 86) and improvements of the underlying theory regarding, for example, the atomic orbital basis set, the level of multipole approximation and the treatment of the important electrostatic and dispersion interactions. A common feature of most members is their consistent parameterization on accurate gas phase theoretical reference data for geometries, vibrational frequencies and noncovalent interactions, which are the primary properties of interest in typical applications to systems composed of up to a few thousand atoms. Further specialized versions were developed for the description of electronic spectra and corresponding response properties. Besides a provided common theoretical background with some important implementation details in the efficient and free xtb program, various benchmarks for structural and thermochemical properties including (transition‐)metal systems are discussed. The review is completed by recent extensions of the model to the force‐field (FF) level as well as its application to solids under periodic boundary conditions. The general applicability together with the excellent cost‐accuracy ratio and the high robustness make the xTB family of methods very attractive for various fields of computer‐aided chemical research. This article is categorized under: Electronic Structure Theory > Ab Initio Electronic Structure Methods Electronic Structure Theory > Semiempirical Electronic Structure Methods Software > Quantum Chemistry

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“…The use of QM/MM potentials in the MD algorithms is an attractive option; however, it is important to maintain a high accuracy level of quantum chemical methods in such QM/MM MD applications. Recent advances in interfacing [ 9 ] the MD package NAMD [ 10 , 11 ] with the quantum chemical package TeraChem [ 12 ]—which is highly efficient on GPUs—promise new achievements in modeling enzyme-catalyzed reactions. It is feasible to apply atom-centered basis sets of 6-31G** or cc-pvdz quality and to use a variety of hybrid functionals of the density functional theory (DFT) in calculations of energies and forces in QM parts and commonly accepted force field parameters in MM parts.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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TeraChem: A graphical processing unit‐accelerated electronic structure package for large‐scale ab initio molecular dynamics

Cited by 213 publications

References 143 publications

Boronic Acids as Prospective Inhibitors of Metallo-β-Lactamases: Efficient Chemical Reaction in the Enzymatic Active Site Revealed by Molecular Modeling

Boronic Acids as Prospective Inhibitors of Metallo-β-Lactamases: Efficient Chemical Reaction in the Enzymatic Active Site Revealed by Molecular Modeling

Extended tight‐binding quantum chemistry methods

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

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