Deciphering the Allosteric Process of the Phaeodactylum tricornutum Aureochrome 1a LOV Domain

The conformational-driven allosteric protein diatom Phaeodactylum tricornutum aureochrome 1a (PtAu1a) differs from other light-oxygen-voltage (LOV) proteins for its uncommon structural topology. The mechanism of signaling transduction in the PtAu1a LOV domain (AuLOV) including flanking helices remains unclear because of this dissimilarity, which hinders the study of PtAu1a as an optogenetic tool. To clarify this mechanism, we employed a combination of tree-based machine learning models, Markov state models, machine-learning-based community analysis, and transition path theory to quantitatively analyze the allosteric process. Our results are in good agreement with the reported experimental findings and reveal a previously overlooked Cα helix and protein linkers as important in promoting the protein conformational changes. This integrated approach can be considered as a general workflow and applied on other allosteric proteins to provide detailed information about their allosteric mechanisms.