Devising analysis tools for elucidating the regulatory mechanism of complex enzymes has been a challenging task for many decades. It generally requires the determination of the structural-dynamical information of protein solvent systems far from equilibrium over multiple length and time scales, which is still difficult both theoretically and experimentally. To cope with the problem, we introduce a full-residue space multiscale simulation method based on a combination of the kinetic Monte Carlo and molecular dynamics techniques, in which the rates of the rate-determining processes are evaluated from a biomolecular forcefield on the fly during the simulation run by taking into account the full space of residues. To demonstrate its reliability and efficiency, we explore the light-induced functional behavior of the full-length phototropin1 from Chlamydomonas reinhardtii (Cr-phot1) and its various subdomains. Our results demonstrate that in the dark state the light oxygen voltage-2-Jα (LOV2-Jα) photoswitch inhibits the enzymatic activity of the kinase, whereas the LOV1-Jα photoswitch controls the dimerization with the LOV2 domain. This leads to the repulsion of the LOV1-LOV2 linker out of the interface region between both LOV domains, which results in a positively charged surface suitable for cell–membrane interaction. By contrast, in the light state, we observe that the distance between both LOV domains is increased and the LOV1-LOV2 linker forms a helix–turn–helix (HTH) motif, which enables gene control through nucleotide binding. Finally, we find that the kinase is activated through the disruption of the Jα-helix from the LOV2 domain, which is followed by a stretching of the activation loop (A-loop) and broadening of the catalytic cleft of the kinase. Proteins 2014; 82:2018–2040. © 2014 Wiley Periodicals, Inc.