Cooperative protein–solvent tuning of proton transfer energetics: carbonic anhydrase as a case study

Literature Information

Publication Date 2020-08-12
DOI 10.1039/D0CP03652H
Impact Factor 3.676
Authors

Laura Zanetti-Polzi, Massimiliano Aschi, Isabella Daidone


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Abstract

We investigate the coupling between the proton transfer (PT) energetics and the protein–solvent dynamics using the intra-molecular PT in wild type (wt) human carbonic anhydrase II and its ten-fold faster mutant Y7F/N67Q as a test case. We calculate the energy variation upon PT, and from that we also calculate the PT reaction free energy, making use of a hybrid quantum mechanics/molecular dynamics approach. In agreement with the experimental data, we obtain that the reaction free energy is basically the same in the two systems. Yet, we show that the instantaneous PT energy is on average lower in the mutant possibly contributing to the faster PT rate. Analysis of the contribution to the PT energetics of the solvent and of each protein residue, also not in the vicinity of the active site, provides evidence for electrostatic tuning of the PT energy arising from the combined effect of the solvent and the protein environment. These findings open up a way to the more general task of the rational design of mutants with either enhanced or reduced PT rate.

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Source Journal

Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics
CiteScore: 5.5
Self-citation Rate: 10.3%
Articles per Year: 3036

Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.

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