"Polarization effects stabilize bacteriorhodopsin's chromophore binding pocket:
A molecular dynamics study."Galina Babitzki, Robert Denschlag, Paul Tavan
J. Phys. Chem. B 113, 10483–10495 (2009)
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 non-polarizable 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.
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