Computational studies of the early intermediates of the bacteriorhodopsin photocycle

Abstract

Starting from a refined model of bacteriorhodopsin's ground state, alternative models of the K and L intermediates with retinal in either 13- cis or 13–14- dicis configuration have been generated by molecular dynamics simulations. All models have been submitted to electrostatic calculations in order to determine the pK 1 2 values of particular residues of interest in the active site. Our pK 1 2 calculations for the refined ground state can reestablish our former results, this time without adjusting the intrinsic p K of the Schiff base. For the K intermediate the electrostatic calculations show no significant change in the pK 1 2 values compared to the ground state for most of the titrating groups in the active site. For the L intermediate where retinal possesses a 13- cis configuration, we found that electrostatic factors decrease the pK 1 2 value of the Schiff base by 4–5 p K-units compared to the ground state. The calculations suggest that changes of the electrostatic environment via a pure 13- cis model are sufficient to produce a p K reduction of the Schiff base that will promote subsequent proton transfer steps.