Migratory birds seasonally travel long distances thanks to the ability to detect the direction of the Earth’s magnetic field. The candidate magnetoreceptor at the basis of this capacity is widely thought to be the FAD-binding protein Cryptochrome 4 (Cry4).
The behavior of Cry4 is determined by an electron transfer chain triggered by the photo-excitation of FAD and involving four adjacent tryptophans (Trp). In particular, the effect of the transfer of one electron along the chain is the reduction of FAD to its radical anionic form and the oxidation of a TrpH, leading to the production of the intermediate radical pair [FAD•– TrpH•+]. This can undergo a change in protonation that brings FAD to its semiquinone form, with the formation of the radical pair [FADH• Trp•], a long-lived state supposedly at the basis of Cry4’s signaling cascade.
Recently, absorption differences have been measured between the Cry4 proteins of European robins (migratory) and pigeons (sedentary), supporting the hypothesis of migratory birds' Cry4 being more sensitive to the magnetic field.
In this work, focusing on Cry4 from robins and pigeons, we performed Molecular Dynamics simulations and demonstrated that such difference is not associated to major structural differences between the two proteins.
Moreover, we characterized the photophysics of robins' Cry4. We derived the kinetic constants of the electron transfer steps under Marcus Theory, obtaining the energies of the radical states formed along the chain through excited state SCF calculations, and treating the system under a QM/MMPol model, with the residues involved in the chain endowed with a QM description and the environment atoms treated classically
