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Photoactivation of Cryptochromes Invokes Competing Inter- and Intramolecular Electron Transfer

Tazhigulov, Ruslan N. and Provazza, Justin and Coker, David F. and Bravaya, Ksenia B. (2020) Photoactivation of Cryptochromes Invokes Competing Inter- and Intramolecular Electron Transfer. . (Unpublished)

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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.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper
Tazhigulov, Ruslan N.0000-0002-0679-3078
Bravaya, Ksenia B.0000-0002-5033-8240
Additional Information:The content is available under CC BY NC ND 4.0 License. This work was supported by Boston University, Department of Chemistry, and in part through computational resources provided by Boston University Shared Computing Cluster. R.N.T. and K.B.B. would like to thank Prof. Shirin Faraji (University of Groningen) for providing Q-Chem/GROMACS interface adapted for this work. R.N.T. and K.B.B. also thank Dr. MiKyung Lee for her help with initial setup of PLDM simulations. D.F.C. acknowledges support for this research from the National Science Foundation under Grant No. CHE-1665367. R.N.T. and J.P. acknowledge support from the Molecular Sciences Software Institute under Grant No. ACI-1547580. The authors have no conflict of interest to declare.
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Boston UniversityUNSPECIFIED
Subject Keywords:photoinduced electron transfer; ultrafast electron transfer dynamics; cryptochrome; protein; semiclassical path integral-based dynamics; model Hamiltonian; QM/MM; polarizable force field; effective fragment potential
Record Number:CaltechAUTHORS:20210709-225304373
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109772
Deposited By: Tony Diaz
Deposited On:09 Jul 2021 23:02
Last Modified:16 Nov 2021 19:37

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