A Multiscale Simulation Framework for Elucidating Photochemical Structure-Activity Relationships of Photoswitchable Ligands in Complex Biomolecular Environments.

ABSTRACT: Predicting the photochemical structure-activity relationships (photo-SAR) of photoswitchable ligands in complex biomolecular environments remains a great challenge due to intricate protein-ligand interactions, strong electron correlation in multiple electronic states, coupled nuclear and electronic dynamics, and protein conformational flexibility. To bridge this gap, here we develop a unified multiscale simulation framework that integrates first-principles nonadiabatic dynamics, excited-state enhanced sampling, and ground-state alchemical free-energy calculations. We applied this approach to photostatins (PSTs), a class of photoswitchable tubulin inhibitors with promising light-regulated anticancer bioactivity, and validated our predictions against extensive experimental data, including ul

SUBMITTER: Bakhtiiari A 

PROVIDER: S-EPMC12690598 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature