Proton release pathway in bacteriorhodopsin: Molecular dynamics and electrostatic calculations

We use molecular dynamics, electrostatic, and quantumchemical calculations to discuss chromophore and protein structural changes as well as proton transfer pathways in the first half of the bacteriorhodopsin photocycle. A model for the molecular mechanism is presented, which accounts for the complex pH dependence of the proton release and uptake pattern found for the M intermediates. The results suggest that transient transfer of the Schiff base proton to a nearby tightly bound water molecule is the primary step, which is accompanyied by dissipation of free energy to the protein. From there, the energetically most favorable proton transfer is to aspartate D85. Arginine R82 is involved in the protein reorientation switch, which catalyzes the pK_a reduction of glutamate E204. This residue is, therefore, identified as extracellular proton release group whose acid base equilibrium regulates the pH‐dependent splitting of the photocycle. © 1994 John Wiley & Sons, Inc.