TCB Publications - Abstract

William Humphrey, Dong Xu, Mordechai Sheves, and Klaus Schulten. Molecular dynamics study of the early intermediates in the bacteriorhodopsin photocycle. Journal of Physical Chemistry, 99:14549-14560, 1995.

HUMP95 The early stages of the bacteriorhodopsin photocycle, including the $J_{625}$, $K_{590}$, and $L_{550}$ intermediates and the role of water molecules within the protein interior, are studied by means of molecular dynamics simulations. Our calculations examine two models for the excited state potential surface governing the observed all-trans $\rightarrow$13-cis photoisomerization, one surface hindering a $C_{14}$$-C_{15}$ single bond co-rotation, the other surface allowing such co-rotation. The investigations use as a starting structure a model bacteriorhodopsin based on electron-microscopy studies and subsequent the molecular dynamics refinement. The following questions are addressed: How does the binding site guide retinal photoisomerization? How does the photoisomerization depend on features of the excited state potential surface? Can one recognize a $J_{625}$ intermediate? How does water participate in the early part of the pump cycle? How is the initial photoreaction affected by a lowering of temperature? To model the quantum yield, i.e., the dependence of the dynamics on initial conditions, 50 separate isomerization trials are completed for each potential surface, at both 300 K and 77 K, the trials distinguished by different initial, random velocity distributions. From these trials emerge, beside all-trans retinal, three different photoproducts as candidates for the $K_{590}$ intermediate: (1) 13-cis retinal, with the Schiff base proton oriented toward Asp-96; (2) 13-cis retinal, highly twisted about the $C_{6}-C_{7}$ bond, with the Schiff base proton oriented perpendicular to the membrane normal; (3) 13, 14-dicis retinal with the Schiff base proton oriented towards the extracellular side. Two candidates for the $K_{590}$ intermediate, case (2) and case (3) above, were subjected to simulated annealing to determine corresponding $L_{550}$ structures. We suggest that photoproduct (2) above most likely represents the true $K_{590}$ intermediate. Water molecules near the Schiff base binding site are found to play a crucial role in stabilizing the $K_{590}$ state and in establishing a pathway for proton transfer to Asp-85.

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