Rotational isomeric state model, conformational changes

More than 30 years ago Warshel proposed, on the basis of semiempirical simulations, an isomerization mechanism that could explain how this process can occur in the restricted space of the Rh binding pocket (Warshel 1976). Since two adjacent double bonds were found to isomerize simultaneously the mechanism reveal a so-called bicycle pedal motion. Due to the concerted rotation of two double bonds in opposite directions the overall conformational change is minimized and hence this mechanism was found to be space-saving. The empirical valence bond (EVB) method (Warshel and Levitt 1976) was used to compute the excited state potential energy surface of the chromophore during a trajectory calculation where the steric effects of the protein matrix were modeled by specific restraints on the retinal atoms. Since then, Warshel and his coworkers have improved the model employing better structural data and new computational developments (Warshel and Barboy 1982 Warshel and Chu 2001 Warshel et al. 1991). The main refinement of the bicycle pedal mechanism was that the simultaneous rotation of the adjacent double bonds is aborted at a twist of 40° and leads to the isomerization of only one bond (Warshel and Barboy 1982). 

There are several reasons for reservations about applying the computer extrapolation of crystal structure data for carbohydrates. One is that much of the crystal structure data refer to unsubstituted sugars which are only soluble in hydroxylic or polar solvents where the conformational analysis may be complicated by hydrolysis, isomerism (muta-rotation) (12), or stereospecific solvent interactions which require a more sophisticated model. However, assuming that such chemical changes do not occur or can be suppressed, there still remain questions to be answered before the conformation observed in the crystal can be accepted as a close enough approximation to that of one or more of the rotomers which may predominate in the solution state. (a-L-Sorbose gives an example of the coexistence of two primary alcohol rotameric... 

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