Polarization effects stabilize bacteriorhodopsin's chromophore binding pocket: A molecular dynamics study

J. Phys. Chem. B, 2009, 113, 10483-10495 published on 06.07.2009
J. Phys. Chem.
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.
TU München