Charge Transfer in Proteins
Photolyases belong to the class of photo-reactivating DNA repair enzymes which repair radiation damaged DNA in a cyclic fashion. If not repaired these defects may suppress DNA processing and thus lead to mutation and cell death. Together with the cryptochromes they are part of the super-family of blue-light driven flavoproteins. Photolyases are present predominantly in various microorganisms while cryptochromes can be found in almost all living organisms, from plants and bacteria to animals and also humans. Cryptochromes function as signaling molecules which regulate diverse biological responses such as entrainment of circadian rythms in plants and animals and the regulation of plant growth and development. Furthermore, Cryptochromes have been proposed to function as magnetoreceptors in migratory birds.
Despite their wide range of physilogical function, all proteins of the Cryptochrome/Photolyase-family are highly similar in their threedimensional structure and primary sequence and contain Flavinadeninedinucleotide (FAD) as a cofactor. During the photoactivation reaction an electron is transferred along a chain of evolutionary conserved Tryptophan resdiues to the Flavin cofactor in the sub-nanosecond range. It remains unclear if this process is physiologically relevant in Photolyases but has been suggested to be functionally important in signaling in cryptochromes.
Simulation of electron transfer in these proteins is challenging for several reasons. Protein and solvent provide a highly heterogeneous and dynamic environment which directly influences the electron transfer properties such as site energies and electronic couplings. Furthermore, the timescale of transfer interferes with the timescale of protein relaxation which renders classical theories like Marcus Theory inapplicable. With our direct QM/MM charge transfer approach we make no assumptions about the CT mechanism, seperation of timescales and electron (de)localization. The direct response of the environment to the moving charge is accounted for by performing molecular dynamics simulation using a QM/MM formalism, while the charge is propagated quantum mechanically. This enables us to study the miroscopic properties of the photoactivation reaction and to predict reaction pathways and reaction mechanisms in proteins of photolyase/cryptochrome family.