The Mechanism of Channel Opening of Anion Channelrhodopsin GtACR1: A Molecular Dynamics Simulation

Guillardia theta anion channelrhodopsin 1 (GtACR1) is a widely used inhibitor of optogenetics with unique conductance mechanisms and photochemistry. However, the molecular mechanism light-gated conduction poorly understood without crystal structure for intermediate state. In this study, we built dark-state model based on retinal isomerized by twisting C12-C13=C14-C15 dihedral step using dynamics simulation. The conformational changes revealed all-trans to 13-cis photoisomerization chromophore cannot open channel. There no water influx, pre-opened K-like after formed. During opening ion channel, proton transfer occurs between E68 D234. Steered (SMD) umbrella sampling indicated that D234 were key residues chloride-ion conducting. We propose revised channel pathway GtACR1 analyzing (de)protonation Reprotonation will result in two different early L intermediates, named L1-like L1‘-like, which correspond L1 L1‘ intermediates reported recent study. Simulation results showed may convert parallel paths into L1‘-like L2-like states. This provides details as well.