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submitted on 06.07.2020 and posted on 07.07.2020by Ruslan N. Tazhigulov, Justin Provazza, David Coker, Ksenia B. Bravaya
Growing experimental and theoretical evidence points to the key role of cryptochrome proteins in magnetoreception by migratory birds and insects. Cryptochrome photoactivation is achieved through a cascade of electron transfer events leading to formation of a long-lived spin-correlated radical pair. The electron transfer cascade is initiated by photoexcitation of the FAD cofactor and subsequent electron transfer through three conserved tryptophan residues, the so-called tryptophan triad. Presence of ATP was shown to increase the yield of the semireduced form of FAD. While electron transfer through the tryptophan triad is well characterized by both theoretical and experimental methods, the effects of ATP binding are still not well understood. The present work aims to unravel the mechanism of ultrafast photoinduced electron transfer in a cryptochrome protein with a focus on effects of ATP on the FAD photoreduction process. Photoinduced electron transfer is described by means of state-of-the-art theoretical methods: a hybrid quantum-classical polarizable embedding scheme is utilized to accurately parameterize a generalized local excited/charge transfer state system-bath model Hamiltonian and the photoinduced electron transfer process is described by a semiclassical path integral-based dynamics method. The results draw attention to the crucial role of the intramolecular electron transfer from adenine to the flavin moiety of the FAD cofactor for formation of the semireduced form of FAD, providing an explanation for the increased yield of the semireduced form in the presence of the cellular metabolites in vitro and in vivo.