title: Polarization effects stabilize bacteriorhodopsin's chromophore binding pocket: a molecular dynamics study.
abstract: Hybrid methods, which combine a quantum mechanical description of a chromophore by density functional theory (DFT) with a molecular mechanics (MM) model of the surrounding protein binding pocket, can enable highly accurate computations of the chromophore's in situ vibrational spectra. As a prerequisite, one needs a MM model of the chromophore-protein complex, which allows a correct sampling of its room-temperature equilibrium fluctuations by molecular dynamics (MD) simulation. Here, we show for the case of bacteriorhodopsin (BR) that MM-MD descriptions with standard nonpolarizable force fields entail a collapse of the chromophore binding pocket. As demonstrated by us, this collapse can be avoided by employing a polarized MM force field derived by DFT/MM hybrid computations. The corresponding MD simulations, which are complemented by a novel Hamiltonian replica exchange approach, then reveal a structural heterogeneity within the binding pocket of the retinal chromophore, which mainly pertains to the structure of the lysine chain covalently connecting the retinal chromophore with the protein backbone.
authors.affiliation: Theoretische Biophysik, Lehrstuhl for Biomolekulare Optik, Ludwig-Maximilians-Universität, Oettingenstr. 67, 80538 München, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Babitzki
authors.forename: R
authors.initials: R
authors.lastname: Denschlag
authors.forename: P
authors.initials: P
authors.lastname: Tavan
mesh_terms: D001436:Bacteriorhodopsins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D011789:Quantum Theory; D013055:Spectrophotometry, Infrared; D013997:Time Factors
chemical_list: D001436:Bacteriorhodopsins