Mechanism of photoinduced electron transfer from tryptophanes to the excited isoalloxazine in animal-like cryptochrome from Chlamydomonas reinhardtii: Molecular dynamics simulation and molecular orbital studies

Cryptochrome from a green alga Chlamydomonas reinhardtii binds flavin adenine dinucleotide (FAD) as a cofactor in a stacked form. The protein structures of the cryptochrome in solution were obtained by means of molecular dynamics simulation (MDS). Mechanisms of photoinduced electron transfer from aromatic chromophores including adenine to the excited isoalloxazine were quantitatively studied with the MDS structures and an electron transfer theory, using the reported experimental rate. The rates were fastest from Trp399, followed by Trp354, Trp332, Trp376, Trp401, Trp294, and adenine. The slower rate from Trp401 despite of the short dis-tance was elucidated with much difference in a net electrostatic energy between the ion-pair and ionic groups in the protein, compared to that in Trp399. The static dielectric constant near isoalloxazine was quite high (7.95), which should be related to a higher number of water molecules near isoalloxazine, compared to those in other non-photoactive flavoproteins. Charge transfer (CT) interactions between isoalloxazine and Trp399 or other Trps (Trp354, Trp332, Trp376, Trp401) were studied by means of a semi-empirical molecular orbital (MO) method. The mean charges transferred from Trps to Iso* over 46 snapshots were-0.514 in Trp399,-0.042 in Trp354, and-0.216 in Trp332,-0.068 in Trp376, and-0.155 in Trp401, which were qualitatively in accordance with the results of photoinduced electron transfer rates. The effect of polarity of the medium on CT interaction was examined with the MO method. The amount of charge transferred from Trp399 to Iso* in the Iso* -Trp399 system decreased with static dielectric constant in the range of 2 to 30.