What Accounts for the Different Function in Photolyases and Cryptochromes: A Computational Study of Critical Events in the Protein Active Site

In the current work, we present a combination of various classical and quantum computational protocols to unveil the molecular mechanism of FAD protonation in E. coli photolyase and its mutant. A direct comparison to our previous study on the plant cryptochrome clearly shows the great influence of the electrostatic environment and the flexibility of the FAD pocket on the proton transfer mechanism. Additionally, we propose a proton transfer pathway for WT E. coli photolyase consistent with experimental observations. Taken together, our results and previous experimental data provide a comprehensive picture about the functional differentiation in the cryptochrome-photolyase family.