| dc.description.abstract | Biological magnetoreception, a sensory modality most notably exhibited by migratory birds, is one of the most intriguing yet still poorly understood phenomena of the emerging field of quantum biology. Thought to arise from the quantum spin dynamics of a photo-initiated radical pair or triad in the ocular Cryptochrome protein, magnetoreception still has no definitive mechanism, identity or number of reactant radicals.
Motivated by the recent formulation of a theoretically more sensitive mechanism, implicating 3 radicals instead of the commonly postulated flavin/tryptophan pair, as well as by experimental results suggesting the involvement of radical species formed later in the flavin photocycle, we report in this thesis an investigation into the magnetosensitivity of a FADH•/O2•-/Y• triad, formed in the so-called "dark reoxidation" of cryptochrome 4, within the context of the scavenging mechanism, whereby the spin dynamics of a primary radical pair are affected by a third, "scavenger" radical.
Spin dynamics simulations were employed to identify, within an avian cryptochrome protein structure (Columba livia cryptochrome 4, or clCry4), a tyrosine residue, Y319, realistically able to function as a scavenger in a FADH•/O2•-/Y• radical triad with fast-relaxing superoxide. In an effort to parametrise our spin dynamics model, we computed hyperfine coupling (HFC) tensors for FADH• and FAD•- using Density Functional Theory (DFT). Dynamical effects were incorporated using long Molecular Dynamics (MD) simulations and a cluster model of the flavin chemical environment. It was found that the flavin electronic structure was significantly perturbed by structural fluctuations, and was well-insulated from electronic polarisation.
Superoxide electrostatic trapping at the protein surface was uncovered with the use of MD simulations. 5 chemically relevant binding sites, able to be populated either from the bulk or from a putative formation site inside the crypt, were identified. Binding times, rotational correlation times, and spin relaxation times for a bound O2•- were computed. It was found that 10^2 ns spin relaxation times were possible for 3 of these sites, possibly contributing non-averaged electron-electron dipolar (EED) to the radical triad’s spin dynamics for a significant portion of its lifetime.
Using a spin dynamics simulation model thus parametrised, we verified the ability of Y319 to elicit magnetosensitivity in a more realistic environment. Particularly promising is its ability to deliver significant MFEs across a broad ranges of conditions, with or without superoxide relaxing; this robustness could play a role in delivering a strong, consistent compass reading from an inhomogeneous ensemble of cryptochrome proteins. | en_GB |
