Corticotropin-releasing factor (CRF) and corticotropin-releasing factor receptor (CRFR) play important roles in stress response, including anxiety and depression syndrome. The CRF expression also relates to chronic stress-related hair loss. This study utilizes the world's largest traditional Chinese medicine (TCM) database and molecular dynamics (MD) simulations to investigate novel CRFR inhibitors for treatment of alopecia. The docking and screening from TCM database results indicate the vitamin B2, 3 beta-isodihydrocadambine, and caribine display higher binding affinity than maltose in maltose binding protein (MBP). However, the results of MD simulation shows the caribine-facilitated CRFR approach closer to MBP, the 3D structure conformation of MBP and CRFR complex forms compact structure. Interestingly, the distance between the two proteins is reducing significantly after caribine dock into MBP binding site. Beside, from Ligand channel analysis, the paths of caribine demonstrate that residence time is increased in binding pocket. Hence, our finding suggests that caribine might be a potential lead compound to stimulate MBP and CRFR interaction, and help for baldless therapy in further study.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS;32(10):1613-23.