Combined QM/MM study of the opsin shift in bacteriorhodopsin

Combined quantum mechanical and molecular mechanical (QM/MM) calculations and molecular dynamics simulations of bacteriorhodopsin (bR) in the membrane matrix have been carried out to determine the factors that make significant contributions to the opsin shift. We found that both solvation and interactions with the protein significantly shifts the absorption maximum of the retinal protonated Schiff base, but the effects are much more pronounced in polar solvents such as methanol, acetonitrile, and water than in the protein environment. The differential solvatochromic shifts of PSB in methanol and in bR leads to a bathochromic shift of about 1800 cm−1. Because the combined QM/MM configuration interaction calculation is essentially a point charge model, this contribution is attributed to the extended point‐charge model of Honig and Nakanishi. The incorporation of retinal in bR is accompanied by a change in retinal conformation from the 6‐s‐cis form in solution to the 6‐s‐trans configuration in bR. The extension of the π‐conjugated system further increases the red‐shift by 2400 cm−1. The remaining factors are due to the change in dispersion interactions. Using an estimate of about 1000 cm−1 in the dispersion contribution by Houjou et al., we obtained a theoretical opsin shift of 5200 cm−1 in bR, which is in excellent agreement with the experimental value of 5100 cm−1. Structural analysis of the PSB binding site revealed the specific interactions that make contributions to the observed opsin shift. The combined QM/MM method used in the present study provides an opportunity to accurately model the photoisomerization and proton transfer reactions in bR. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 96–105, 2002