Reversible Proton Transfer Dynamics in Bacteriorhodopsin
Y. S. Lee, Morris Krauss
Proton transfer in bacteriorhodopsin from the cytoplasm 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 photocycle late M state to the N state. Ab initio dynamics using the CHARMM/GAMESS methodology is used to simulate the transfer of the proton through a hydrophobic channel. 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 while treating rest of the atoms molecular mechanically. Structural transformation occurs in the M state that results in a channel between the asp96 and Schiff base allowing a water chain between these groups. A chain of four waters from asp96 to the Schiff base N with one branching water supports proton transfer as a concerted event in about 3.5 ps with neutral asp85. Dynamic transfer of the proton from asp96 to the nearest water initiates the organization of a strongly hydrogen bonded ionic water chain conducive to the transfer of the proton to the Schiff base N. Proton transfer is also observed from the Schiff base back to asp96 demonstrating that there is no effective barrier to proton transfer larger than kT within the close-coupled hydrogen bond network. The fifth water that branches from the four water chain is also hydrogen bonded to back-bone carbonyls. The binding of this water to the chain can dynamically inhibit the proton transfer.
Journal of Molecular Structure
Sp. Iss. 1-3
September 16-21, 2003
15th International Conference on Horizons in Hydrogen Bond Research
ab initio QMMM molecular dynamics, bacteriorhodopsin, hydrogen bond network, proton wire, reversible proton transfer