Development of a microscopic gas diffusion-reaction model for a H2 producing biocatalyst
Lead Research Organisation:
University of Cambridge
Department Name: Chemistry
Abstract
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Publications
Carter JW
(2013)
Engineering folding dynamics from two-state to downhill: application to ?-repressor.
in The journal of physical chemistry. B
De Sancho D
(2015)
Identification of Mutational Hot Spots for Substrate Diffusion: Application to Myoglobin.
in Journal of chemical theory and computation
Kemplen KR
(2015)
The response of Greek key proteins to changes in connectivity depends on the nature of their secondary structure.
in Journal of molecular biology
Kubas A
(2017)
Mechanism of O2 diffusion and reduction in FeFe hydrogenases.
in Nature chemistry
Kubas A
(2014)
Aerobic damage to [FeFe]-hydrogenases: activation barriers for the chemical attachment of O2.
in Angewandte Chemie (International ed. in English)
Rogers JM
(2014)
Interplay between partner and ligand facilitates the folding and binding of an intrinsically disordered protein.
in Proceedings of the National Academy of Sciences of the United States of America
Zheng W
(2015)
Dependence of internal friction on folding mechanism.
in Journal of the American Chemical Society
| Description | Hydrogenases are natural hydrogen-producing enzymes. Their biotechnological exploitation, however, has been hampered by their extreme oxygen sensitivity. We have been studying ways to modify these enzymes with the aim of increasing the oxygen tolerance of this enzyme are discussed. We have identified the mechanisms by which hydrogenases are accessed from the bulk solvent. This has allowed determining specific amino-acid residues that act as gates for the gas molecules to break in. We have predicted mutations that would block these gates. The predicted mutations indeed inhibit the degradation of the protein active site. |
| Exploitation Route | We anticipate that these results will be use by biotechnological companies interested in hydrogen production. |
| Sectors | Chemicals,Energy,Environment,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | Hydrogenases are enzymes that catalyze hydrogen oxidation and reduction. In this project, we characterised the chemical process underlying this reaction. Specifically, we combined quantum mechanical calculations and molecular dynamics simulations, together with experiment, to explore the reaction mechanism of oxygen reduction and its diffusion pathways into one of these enzymes. This work was published in 2017 in a high profile paper in Nature Chemistry. This work has received 76 citations. Since then, our collaboration with the experimental group in Marseille went into a hiatus, but the PDRA has recently another collaboration using the very methodologies developed in this project. |
| First Year Of Impact | 2014 |
| Sector | Chemicals |
| Impact Types | Cultural |
| Description | Voltammetry |
| Organisation | Aix-Marseille University |
| Country | France |
| Sector | Academic/University |
| PI Contribution | We contributed classical molecular simulation methods and algorithms for the construction of kinetic models from simulation data. This allowed predicting mutations that would maximally affect the rates of inhibition of hydrogenase enzymes. |
| Collaborator Contribution | Our partners in France contributed their expertise in protein film voltammetry. Using this technique they can measure currents corresponding to the catalysis of the hydrogenase enzyme. Leger and his team measured changes in rate coefficients for the catalysis by hydrogenases from mutations that were predicted by us. The effect predicted from the simulations was indeed confirmed in the experimental work. This result suggests new possible avenues for exploiting clean energy production using this type of enzymes. |
| Impact | Publications: PMID : 27995927 |
| Start Year | 2014 |