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Computational molecular bioenergetics


Electron transport chain enzymes in mitochondria and bacteria are equipped with transition metal-based prosthetic groups involved in essential oxidoreduction processes. In this project we propose to elucidate catalytic mechanisms and the structural stability of metal cofactors bound in these proteins. We will investigate the mechanisms of proton-electron coupled transfer (PCET) reactions of succinate and ubiquinol substrates, catalyzed by iron-sulfur clusters linked to respiratory complexes II (or succinate dehydrogenase) and III (or cytochrome bc1), respectively. We will also study the structural stability and mechanochemical activation of zinc-thiolate and cadmium-thiolate covalent bonds through the forced unfolding of the metallothionein-III protein. There is great interest in these reaction mechanisms in basic molecular and applied biophysical research for new biomaterials.We will apply and develop advanced methods in electronic structure calculation and molecular simulation, particularly hybrid potentials of quantum chemistry and molecular mechanics (QM/MM). We are pioneers and one of the only groups in Brazil that use these techniques to study enzymatic mechanisms. In particular, the computational simulation of metal complexes in solution or linked to macromolecules is still a challenge that we intend to tackle in this project by implementing new approximations for redox potential calculation and optimization of constrained molecular orbitals. The study of the forced unfolding of metallothionein-III will be conducted in direct comparison to atomic force microscopy (AFM) experiments.The research proposed here will be conducted by PhD students already members of the laboratory, as well as the principal researcher and international collaborators in France and China. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CURTOLO, FELIPE; ARANTES, GUILHERME M. Mechanisms for Flavin-Mediated Oxidation: Hydride or Hydrogen-Atom Transfer?. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 60, n. 12, p. 6282-6287, DEC 28 2020. Web of Science Citations: 0.

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