ArticleJournal of chemical theory and computation2016
Computationally Efficient Multiscale Reactive Molecular Dynamics to Describe Amino Acid Deprotonation in Proteins.
Article in Journal of chemical theory and computation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Multiscale Responsive Kinetic Modeling: Quantifying Biomolecular Reaction Flux under Varying Electrochemical Conditions.bioRxiv : the preprint server for biology · 2024Article
- Molecular Dynamics Simulation of Complex Reactivity with the Rapid Approach for Proton Transport and Other Reactions (RAPTOR) Software Package.The journal of physical chemistry. B · 2024Article
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Transient water wires mediate selective proton transport in designed channel proteins.Nature chemistry · 2023Article
- Hybrid Quantum Mechanical/Molecular Mechanical Methods For Studying Energy Transduction in Biomolecular Machines.Annual review of biophysics · 2023Review
- The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter.Biophysical journal · 2023Article
- Generalized Transition State Theory Treatment of Water-Assisted Proton Transport Processes in Proteins.The journal of physical chemistry. B · 2022Article
- Interplay of Hydration and Protonation Dynamics in the K-Channel of Cytochrome c Oxidase.Biomolecules · 2022Article
- Accurate pThe journal of physical chemistry. B · 2022Article
- Proton coupling and the multiscale kinetic mechanism of a peptide transporter.Biophysical journal · 2022Article
- Advanced Theory and Simulation to Guide the Development of COACS omega · 2022Review
- Multiscale kinetic analysis of proteins.Current opinion in structural biology · 2022Review
- Multiscale Simulation of an Influenza A M2 Channel Mutant Reveals Key Features of Its Markedly Different Proton Transport Behavior.Journal of the American Chemical Society · 2022Article
- A quantitative paradigm for water-assisted proton transport through proteins and other confined spaces.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Accurate and Transferable Reactive Molecular Dynamics Models from Constrained Density Functional Theory.The journal of physical chemistry. B · 2021Article
- Toward a Multipathway Perspective: pH-Dependent Kinetic Selection of Competing Pathways and the Role of the Internal Glutamate in ClThe journal of physical chemistry. B · 2021Article
- Deactivation blocks proton pathways in the mitochondrial complex I.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics.Journal of the American Chemical Society · 2020Article
- Multiscale Simulation Reveals Passive Proton Transport Through SERCA on the Microsecond Timescale.Biophysical journal · 2020Article
- A Computational Swiss Army Knife Approach to Unraveling the Secrets of Proton Movement through SERCA.Biophysical journal · 2020Article
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4 authors.
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Abstract
An important challenge in the simulation of biomolecular systems is a quantitative description of the protonation and deprotonation process of amino acid residues. Despite the seeming simplicity of adding or removing a positively charged hydrogen nucleus, simulating the actual protonation/deprotonation process is inherently difficult. It requires both the explicit treatment of the excess proton, including its charge defect delocalization and Grotthuss shuttling through inhomogeneous moieties (water and amino residues), and extensive sampling of coupled condensed phase motions. In a recent paper (J. Chem. Theory Comput. 2014, 10, 2729-2737), a multiscale approach was developed to map high-level quantum mechanics/molecular mechanics (QM/MM) data into a multiscale reactive molecular dynamics (MS-RMD) model in order to describe amino acid deprotonation in bulk water. In this article, we extend the fitting approach (called FitRMD) to create MS-RMD models for ionizable amino acids within proteins. The resulting models are shown to faithfully reproduce the free energy profiles of the reference QM/MM Hamiltonian for PT inside an example protein, the ClC-ec1 H(+)/Cl(-) antiporter. Moreover, we show that the resulting MS-RMD models are computationally efficient enough to then characterize more complex 2-dimensional free energy surfaces due to slow degrees of freedom such as water hydration of internal protein cavities that can be inherently coupled to the excess proton charge translocation. The FitRMD method is thus shown to be an effective way to map ab initio level accuracy into a much more computationally efficient reactive MD method in order to explicitly simulate and quantitatively describe amino acid protonation/deprotonation in proteins.
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