Abstract
All-atom molecular dynamics (MD) studies have offered first insights into the structural dynamics of cryptochrome but are limited to a short time scale due to large computational demands. Here, we employ coarse-grained MD simulations to investigate the emergence of long-lived states and conformational changes in pigeon cryptochrome 4. Our coarse-grained simulations complete the picture by permitting observation on a significantly longer time scale. We observe conformational transitions in the phosphate-binding loop of pigeon cryptochrome 4 upon activation and identify prominent motions in residues 440–460, suggesting a possible role as a signaling state of the protein or as a gated interaction site for forming protein complexes that might facilitate downstream processes. Furthermore, a conformational switch of the third and fourth tryptophane of the electron transfer cascade was observed, which merits further scrutiny. The findings highlight the importance of considering longer time scales in studying cryptochrome dynamics and magnetoreception. Further exploration of these conformational changes and their functional implications may contribute to a deeper understanding of the molecular mechanisms of magnetoreception in birds.