Ion Transport from Physics to Physiology: the Missing Rungs in the Ladder
Modelling channel opening in Channelrhodopsin-2Albert Ardevol
Max-Planck Institute for Biophysics Frankfurt, Germany
Channelrhodopsins are type-I rhodopsin proteins found in green algae that function as sensory photoreceptors and turn into ion channels under illumination. Upon light absorbance, the retinal isomerization induces a conformational change on the protein that opens a channel through which ions can pass. However, in contrast to closely related bacteriorhodopsins or halorhodopsins, very little is known about their structure, light cycle and mechanism of action. Using the X-ray structure of the C1C2 chimera1 as reference, we used MD simulations to model the closed state of the wild type channelrhodopsin-2 (ChR2). We validated the structure by comparison to the spectral properties of the chromophore, the backbone and the carboxylic acid residues of the active site.2 We show that the agreement with the experimental data is improved by using a force-matching force-field3 for the chromophore in the ChR2 environment. Using metadynamics, we have simulated the photo-isomerization of the retinal, which induces an early formation of a continuous solvated pore through the protein. We analyzed the mechanism of formation, the structure of the channel and the mechanism of ion transport and compared it to experimental observations.