Flexible-Boundary Quantum-Mechanical/Molecular-Mechanical Calculations:  Partial Charge Transfer between the Quantum-Mechanical and Molecular-Mechanical Subsystems

Zhang, Yan; Lin, Hai

doi:10.1021/ct700296x

Cited by 51 publications

(43 citation statements)

References 79 publications

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“…In fact, both the QM and the MM regions should polarize each other until self‐consistency is achieved in the charge distribution. However, properly dealing with this effect is a complicated task, as it requires the use of a polarizable MM FF, able to react to a perturbation by the QM region, a feature that is not typically available in current commercial MM FFs, even though some efforts have been reported . Additional difficulties in the implementation of polarized embedding schemes arise from problems in the treatment of the QM/MM boundary and from the much increased computational cost that results from the necessary iterations required for self‐consistency in the charge distribution to be achieved.…”

Section: Types Of Qm/mm Schemesmentioning

confidence: 99%

Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms

Sousa

Ribeiro

Neves

et al. 2016

WIREs Comput Mol Sci

162

118

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Quantum mechanics/molecular mechanics (QM/MM) methods offer a very appealing option for the computational study of enzymatic reaction mechanisms, by separating the problem into two parts that can be treated with different computational methods. Hence, in a QM/MM formalism, the part of the system in which catalysis actually occurs and that involves the active site, substrates and directly participating amino acid residues is treated at an adequate quantum mechanical level to describe the chemistry taking place. For the remaining of the enzyme, which does not participate directly in the reaction, but that typically involves a much larger number of atoms, molecular mechanics is employed, traditionally through the application of a biomolecular force field. When applied with care, QM/MM methods can be used with great advantage in comparing, at a structural and energetic level, different mechanistic proposals, discarding mechanistic alternatives and proposing new mechanistic pathways that are consistent with the available experimental data. With time, diverse flavors within the QM/MM methods have emerged, differing in a variety of technical and conceptual aspects. Hence present alternatives differ between additive and subtractive QM/MM schemes, the type of boundary schemes, and the way in which the electrostatic interactions between the two regions are accounted for. Also, single‐conformation QM/MM, multi‐PES approaches, and QM/MM Molecular Dynamics coexist today, each type with its own advantages and limitations. This review focuses on the application of QM/MM methods in the study of enzymatic reaction mechanisms, briefly presenting also the most important technical aspects involved in these calculations. Particular attention is dedicated to the application of the single‐conformation QM/MM, multi‐PES QM/MM studies, and QM/MM‐FEP methods and to the advantages and disadvantages of the different types of QM/MM. Recent breakthroughs are also introduced. A selection of hand‐picked examples is used to illustrate such features. WIREs Comput Mol Sci 2017, 7:e1281. doi: 10.1002/wcms.1281 This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Structure and Mechanism > Reaction Mechanisms and Catalysis Electronic Structure Theory > Combined QM/MM Methods

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Section: Types Of Qm/mm Schemesmentioning

confidence: 99%

Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms

Sousa

Ribeiro

Neves

et al. 2016

WIREs Comput Mol Sci

162

118

View full text Add to dashboard Cite

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“…To conclude this review, we would like to bring readers’ attention to one interesting question: can adaptive QM/MM be combined with other multiscale methods? One intriguing development will be to combine the adaptive treatments with the flexible‐boundary embedding scheme . Flexible‐ boundary embedding describes both mutual polarizations and partial charge transfer between the QM and MM subsystems, offering in principle the most sophisticated and most accurate treatment for the electrostatic interactions between the two subsystems.…”

Section: Resultsmentioning

confidence: 99%

Adaptive quantum/molecular mechanics: what have we learned, where are we, and where do we go from here?

Duster

Wang

Garza

et al. 2017

WIREs Comput Mol Sci

Self Cite

108

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Adaptive quantum‐mechanics/molecular‐mechanics (QM/MM) methods feature on‐the‐fly reclassification of atoms as QM or MM during a molecular dynamics (MD) simulation, allowing the location and contents of the QM subsystem to be dynamically updated as needed. Such flexibility is a distinct advantage over conventional QM/MM, where a ‘static’ boundary is retained between the QM and MM subsystems. The ‘dynamic’ boundary in adaptive QM/MM allows a finite‐size QM to sustain simulations with an arbitrary length of time. To ensure smooth transitions between QM and MM, the energy or forces are interpolated. Special treatments are applied so that artifacts are eliminated or minimized. Recent developments have shed light on the relationship between the adaptive algorithms that describe Hamiltonian and non‐Hamiltonian systems. Originally developed to model an ion solvated in bulk solvent, adaptive QM/MM has been enhanced in many aspects, including the treatment of molecular fragments in macromolecules, monitoring molecules entering/leaving binding sites, and tracking proton transfer via the Grotthuss mechanism. Because the size of the QM region can be set as small as possible in adaptive QM/MM, the computational costs can be kept low. Small QM subsystems also facilitate the utilization of high‐level QM theory and long simulation time, which can potentially lead to new insights. WIREs Comput Mol Sci 2017, 7:e1310. doi: 10.1002/wcms.1310 This article is categorized under: Electronic Structure Theory > Combined QM/MM Methods Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods Software > Molecular Modeling

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“…Simple charge equilibrium approach has been implemented to allow the charge transfer between subsystems [76]. However, there are two practical issues should be noted.…”

Section: Qm/mm Methodsmentioning

confidence: 99%

Development and application of ab initio QM/MM methods for mechanistic simulation of reactions in solution and in enzymes

Yang

2009

Journal of Molecular Structure: THEOCHEM

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Determining the free energies and mechanisms of chemical reactions in solution and enzymes is a major challenge. For such complex reaction processes, combined quantum mechanics/molecular mechanics (QM/MM) method is the most effective simulation method to provide an accurate and efficient theoretical description of the molecular system. The computational costs of ab initio QM methods, however, have limited the application of ab initio QM/MM methods. Recent advances in ab initio QM/MM methods allowed the accurate simulation of the free energies for reactions in solution and in enzymes and thus paved the way for broader application of the ab initio QM/MM methods. We review here the theoretical developments and applications of the ab initio QM/MM methods, focusing on the determination of reaction path and the free energies of the reaction processes in solution and enzymes.

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Flexible-Boundary Quantum-Mechanical/Molecular-Mechanical Calculations: Partial Charge Transfer between the Quantum-Mechanical and Molecular-Mechanical Subsystems

Cited by 51 publications

References 79 publications

Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms

Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms

Adaptive quantum/molecular mechanics: what have we learned, where are we, and where do we go from here?

Development and application of ab initio QM/MM methods for mechanistic simulation of reactions in solution and in enzymes

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