title: 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 pK1/2 values of particular residues of interest in the active site. Our pK1/2 calculations for the refined ground state can reestablish our former results, this time without adjusting the intrinsic pK of the Schiff base. For the K intermediate the electrostatic calculations show no significant change in the pK1/2 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 pK1/2 value of the Schiff base by 4-5 pK-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 pK reduction of the Schiff base that will promote subsequent proton transfer steps.
authors.affiliation: Scripps Research Institute, Department of Molecular Biology, La Jolla, CA 92037, USA.
authors.forename: M
authors.initials: M
authors.lastname: Engels
authors.forename: K
authors.initials: K
authors.lastname: Gerwert
authors.forename: D
authors.initials: D
authors.lastname: Bashford
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine; D001224:Aspartic Acid; D001436:Bacteriorhodopsins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D004563:Electrochemistry; D007700:Kinetics; D008958:Models, Molecular; D010777:Photochemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012172:Retinaldehyde / Q000378:metabolism*; D012545:Schiff Bases; D013997:Time Factors; D014443:Tyrosine
chemical_list: D012545:Schiff Bases; D001224:Aspartic Acid; D014443:Tyrosine; D001436:Bacteriorhodopsins; D001120:Arginine; D012172:Retinaldehyde