Proton transfer from the cyctoplasm to the extracellular side is initiated from protonated asp96 in the cytoplasmic region towards the deprotonated Schiff base. This occurs in the transition from the late M photocycle state to the N state. A quantum mechanics/molecular mechanics (QM/MM) model is constructed from the bacteriorhodopsin E204Q mutant crystal structure. Three residues, asp96, asp85, and thr89 as well as most of the retinal chromophore and the Schiff base link of lys216 are treated quantum mechanically and connected to the remaining classical protein through linker atoms. Structural transformation occurs in the M state that result in a channel between the asp96 and Schiff base allowing a water chain between these groups. Since a part of this channel is lined with hydrophobic residues, there has been a question on the mechanism of proton transfer in a hydrophobic channel. Ab initio dynamics using the CHARMM/GAMESS methodology is used to simulate the transfer of the proton through a hydrophobic channel. Once sufficient water molecules are added to the channel to allow the formation of a single chain of waters from asp96 to the Schiff base, the transfer occurs as a fast (less than a picosecond) concerted event. Dynamic transfer of the proton from asp96 to the nearest water initiates the organization of a strongly bonded ionic water chain conducive to the transfer of the proton to the Schiff base N.
Journal of the American Chemical Society
bacteriorhodopsin, hydrophobic channel, proton transfer, QM/MM simulation, retinal, schiff base