Investigating the relationship between protein dynamics and electron transfers (joint IQST-CMS seminar) - Aurelien de la Lande

Electron transfers (ET) are common events occurring in the course of many enzymatic reactions. Numerical approaches can play an important role in complement to experimental studies to uncover the subtle relationships between the thermodynamics and the kinetics aspects of ETs and the protein dynamics. As an illustration, I will first present a computational study of the hydroxylation mechanism of PHM (Peptidylglycine α-Hydroxylating Monooxygenase)1 based on molecular dynamics (MD) simulations with hybrid Density Functional Theory-classical potentials (DFT/MM).2 Our study sheds new light on the catalytic cycle of this enzyme that has the ability to achieve dioxygen-dependent hydroxylation of aliphatic C-H bonds using two uncoupled metal sites between which a long range ET has to occur.3 In a second part I will present a computational study of the primary step of the photoreduction of flavin adenine mononucleotide (FAD) within a cryptochrome of plant.4 These proteins are involved in the regulation of the circadian cycles of plants or mammals, and putatively at the source of the migratory sense of birds.5 A combination of long classical MD simulations, Time-Dependent DFT calculations using long range corrected functionals and searches for empirical tunnelling pathways,6 enabled us to rationalize recent experiments performed by our collaborators.7 1: Osborne R.L.; Klinman, J. P. "Copper Oxygen Chemistry", pp 1-22; 2011, Ed. Karlin, K. D.; Itoh, S. Pub. J. Wiley & Sons. 2: Melía C.; Ferrer S.; Řezáč J.; Parisel O.; Reinaud O.; Moliner V.; de la Lande A. Chem. Eur. J. 2013, 19, 17328 – 17337. 3: de la Lande A.; Parisel O.; Moliner V. J. Am. Chem. Soc. 2007, 129,11700-11707. 4: Chaves, I. et al. Annu. Rev. Plant. Biol. 2011, 62, 335-364. 5: Ritz Th.; Adem S.; Schulten K. Biophys. J. 2000, 78, 707-7018 6: Cailliez F.; Gallois M.; Muller P.; de la Lande A. in preparation 7: Muller P.; Bouly J. -P.; Hitomi K.; Balland V.; Getzoff E. D.; Ritz Th.; Brettel K. Submitted