ReviewBiochimica et biophysica acta2010
Proton transfer function of carbonic anhydrase: Insights from QM/MM simulations.
Review in Biochimica et biophysica acta, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 58 citations in OpenAlex.
- Benchmark Study for Calculations of pKa Values of Metal Ligands in Proteins.Journal of chemical theory and computation · 2026Article
- Carbonic anhydrase under the computational lens: a review of advances, challenges, and future directions.Journal of molecular modeling · 2026Review
- Emerging Role of Deuterium/Protium Disbalance in Cell Cycle and Apoptosis.International journal of molecular sciences · 2023Review
- Frontiers of metal-coordinating drug design.Expert opinion on drug discovery · 2021Review
- Conformational Change of H64 and Substrate Transportation: Insight Into a Full Picture of Enzymatic Hydration of COFrontiers in chemistry · 2021Article
- Redox-coupled proton pumping drives carbon concentration in the photosynthetic complex I.Nature communications · 2020Article
- An Update on the Metabolic Roles of Carbonic Anhydrases in the Model Alga Chlamydomonas reinhardtii.Metabolites · 2018Review
- Analysis of Phosphoryl-Transfer Enzymes with QM/MM Free Energy Simulations.Methods in enzymology · 2018Article
- Regulation and Plasticity of Catalysis in Enzymes: Insights from Analysis of Mechanochemical Coupling in Myosin.Biochemistry · 2017Article
- Coupling Protein Dynamics with Proton Transport in Human Carbonic Anhydrase II.The journal of physical chemistry. B · 2016Article
- QM/MM Analysis of Transition States and Transition State Analogues in Metalloenzymes.Methods in enzymology · 2016Article
- DFTB3 Parametrization for Copper: The Importance of Orbital Angular Momentum Dependence of Hubbard Parameters.Journal of chemical theory and computation · 2015Article
- Parametrization of DFTB3/3OB for magnesium and zinc for chemical and biological applications.The journal of physical chemistry. B · 2015Article
- Microscopic basis for kinetic gating in Cytochrome c oxidase: insights from QM/MM analysis.Chemical science · 2015Article
- Molecular simulation of water and hydration effects in different environments: challenges and developments for DFTB based models.The journal of physical chemistry. B · 2014Article
- Density functional tight binding: values of semi-empirical methods in an ab initio era.Physical chemistry chemical physics : PCCP · 2014Article
- Parameterization of DFTB3/3OB for Sulfur and Phosphorus for Chemical and Biological Applications.Journal of chemical theory and computation · 2014Article
- Benchmark Study of the SCC-DFTB Approach for a Biomolecular Proton Channel.Journal of chemical theory and computation · 2014Article
- Changing hydration level in an internal cavity modulates the proton affinity of a key glutamate in cytochrome c oxidase.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Molecular switches: Hydrazones double down on zinc.Nature chemistry · 2012Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Recent QM/MM analyses of proton transfer function of human carbonic anhydrase II (CAII) are briefly reviewed. The topics include a preliminary analysis of nuclear quadrupole coupling constant calculations for the zinc ion and more detailed analyses of microscopic pK(a) of the zinc-bound water and free energy profile for the proton transfer. From a methodological perspective, our results emphasize that performing sufficient sampling is essential to the calculation of all these quantities, which reflects the well solvated nature of CAII active site. From a mechanistic perspective, our analyses highlight the importance of electrostatics in shaping the energetics and kinetics of proton transfer in CAII for its function. We argue that once the pK(a) for the zinc-bound water is modulated to be in the proper range (approximately 7.0), proton transfer through a relatively well solvated cavity towards/from the protein surface (His64) does not require any major acceleration. Therefore, although structural details like the length of the water wire between the donor and acceptor groups still may make a non-negligible contribution, our computational results and the framework of analysis suggest that the significance of such "fine-tuning" is likely secondary to the modulation of pK(a) of the zinc-bound water. We encourage further experimental analysis with mutation of (charged) residues not in the immediate neighborhood of the zinc ion to quantitatively test this electrostatics based framework; in particular, Phi analysis based on these mutations may shed further light into the relative importance of the classical Grotthus mechanism and the "proton hole" pathway that we have proposed recently for CAII.
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