Cryptochrome magnetoreception: Time course of photoactivation from non-equilibrium coarse-grained molecular dynamics

Magnetoreception, the ability to sense magnetic fields, is widespread in animals but remains poorly understood. The leading model links this ability in migratory birds to the photo-activation of the protein cryptochrome. Magnetic information is thought to induce structural changes in cryptochrome vi...

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Main Authors: Jessica L. Ramsay, Fabian Schuhmann, Ilia A. Solov’yov, Daniel R. Kattnig
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Computational and Structural Biotechnology Journal
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Online Access:http://www.sciencedirect.com/science/article/pii/S2001037024003726
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author Jessica L. Ramsay
Fabian Schuhmann
Ilia A. Solov’yov
Daniel R. Kattnig
author_facet Jessica L. Ramsay
Fabian Schuhmann
Ilia A. Solov’yov
Daniel R. Kattnig
author_sort Jessica L. Ramsay
collection DOAJ
description Magnetoreception, the ability to sense magnetic fields, is widespread in animals but remains poorly understood. The leading model links this ability in migratory birds to the photo-activation of the protein cryptochrome. Magnetic information is thought to induce structural changes in cryptochrome via a transient radical pair intermediate. This signal transduction pathway has been the subject of previous all-atom molecular dynamics (MD) simulations, but insights were limited to short timescales and equilibrium structures. To address this, we developed a non-equilibrium coarse-grained MD simulation approach, exploring cryptochrome’s photo-reduction over 20 replicates of 20 µs each. Our results revealed significant structural changes across the protein, with an overall time constant of 3 µs. The C-terminal (CT) region responded on a timescale of 4.7 µs, followed by the EEE-motif, while the phosphate binding loop (PBL) showed slower dynamics (9 µs). Network analysis highlighted direct pathways connecting the tryptophan tetrad to the CT, and distant pathways involving the EEE and PBL regions. The CT-dynamics are significantly impacted by a rearrangement of tryptophan residues in the central electron transfer chain. Our findings underscore the importance of considering longer timescales when studying cryptochrome magnetoreception and highlight the potential of non-equilibrium coarse-grained MD simulations as a powerful tool to unravel protein photoactivation reactions.
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spelling doaj-art-62578ac4d2ca492aa4fd6f3434b641602024-12-19T10:53:30ZengElsevierComputational and Structural Biotechnology Journal2001-03702024-12-01265869Cryptochrome magnetoreception: Time course of photoactivation from non-equilibrium coarse-grained molecular dynamicsJessica L. Ramsay0Fabian Schuhmann1Ilia A. Solov’yov2Daniel R. Kattnig3Department of Physics, University of Exeter, Stocker Rd., Exeter EX4 4QL, UK; Living Systems Institute, University of Exeter, Stocker Rd., Exeter EX4 4QD, UKNiels Bohr International Academy, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, Copenhagen 2100, DenmarkInstitute of Physics, Carl von Ossietzky Universität Oldenburg, Carl-von-Ossietzky Str. 9–11, Oldenburg 26129, Germany; Research Centre for Neurosensory Science, Carl von Ossietzky Universität Oldenburg, Carl-von-Ossietzky-Str. 9-11, Oldenburg 26129, Germany; Center for Nanoscale Dynamics (CENAD), Carl von Ossietzky Universität Oldenburg, Ammerländer Heerstr. 114–118, Oldenburg 26129, GermanyDepartment of Physics, University of Exeter, Stocker Rd., Exeter EX4 4QL, UK; Living Systems Institute, University of Exeter, Stocker Rd., Exeter EX4 4QD, UK; Corresponding author at: Department of Physics, University of Exeter, Stocker Rd., Exeter EX4 4QL, UK.Magnetoreception, the ability to sense magnetic fields, is widespread in animals but remains poorly understood. The leading model links this ability in migratory birds to the photo-activation of the protein cryptochrome. Magnetic information is thought to induce structural changes in cryptochrome via a transient radical pair intermediate. This signal transduction pathway has been the subject of previous all-atom molecular dynamics (MD) simulations, but insights were limited to short timescales and equilibrium structures. To address this, we developed a non-equilibrium coarse-grained MD simulation approach, exploring cryptochrome’s photo-reduction over 20 replicates of 20 µs each. Our results revealed significant structural changes across the protein, with an overall time constant of 3 µs. The C-terminal (CT) region responded on a timescale of 4.7 µs, followed by the EEE-motif, while the phosphate binding loop (PBL) showed slower dynamics (9 µs). Network analysis highlighted direct pathways connecting the tryptophan tetrad to the CT, and distant pathways involving the EEE and PBL regions. The CT-dynamics are significantly impacted by a rearrangement of tryptophan residues in the central electron transfer chain. Our findings underscore the importance of considering longer timescales when studying cryptochrome magnetoreception and highlight the potential of non-equilibrium coarse-grained MD simulations as a powerful tool to unravel protein photoactivation reactions.http://www.sciencedirect.com/science/article/pii/S2001037024003726CryptochromeMagnetoreceptionRadical pair mechanismProtein dynamicsCoarse-grained molecular dynamicsNetwork model
spellingShingle Jessica L. Ramsay
Fabian Schuhmann
Ilia A. Solov’yov
Daniel R. Kattnig
Cryptochrome magnetoreception: Time course of photoactivation from non-equilibrium coarse-grained molecular dynamics
Computational and Structural Biotechnology Journal
Cryptochrome
Magnetoreception
Radical pair mechanism
Protein dynamics
Coarse-grained molecular dynamics
Network model
title Cryptochrome magnetoreception: Time course of photoactivation from non-equilibrium coarse-grained molecular dynamics
title_full Cryptochrome magnetoreception: Time course of photoactivation from non-equilibrium coarse-grained molecular dynamics
title_fullStr Cryptochrome magnetoreception: Time course of photoactivation from non-equilibrium coarse-grained molecular dynamics
title_full_unstemmed Cryptochrome magnetoreception: Time course of photoactivation from non-equilibrium coarse-grained molecular dynamics
title_short Cryptochrome magnetoreception: Time course of photoactivation from non-equilibrium coarse-grained molecular dynamics
title_sort cryptochrome magnetoreception time course of photoactivation from non equilibrium coarse grained molecular dynamics
topic Cryptochrome
Magnetoreception
Radical pair mechanism
Protein dynamics
Coarse-grained molecular dynamics
Network model
url http://www.sciencedirect.com/science/article/pii/S2001037024003726
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AT iliaasolovyov cryptochromemagnetoreceptiontimecourseofphotoactivationfromnonequilibriumcoarsegrainedmoleculardynamics
AT danielrkattnig cryptochromemagnetoreceptiontimecourseofphotoactivationfromnonequilibriumcoarsegrainedmoleculardynamics