Retinal and Vision

FIGURE 12.15 The attachment of 11-cw-retinal to the protein is via a nitrogen atom (dark, on the far right), called a Schiff base, belonging to the side group of the peptide lysine. Short bonds are dashed (=). The bond involved in the cis-trans isomerization is marked by a star. 

Wald had good reasons to believe that a cis-trans isomerization triggers the signal that reports to the brain that light has been registered. 

We now know, not least from crystallographic studies, that the cis form of the molecule fits well into its cavity and is attached to the protein via the nitrogen atom (Schiff base) of the side chain of the peptide lysine. The cavity does not fit into trans-retinal. But how is it possible to carry out a cis-trans isomerization inside the protein cavity It is well known that protein matter does not allow void space, so it might be expected that the retinal fits exactly. One possibility is that the protein adjusts itself to the changed structure of the molecule, but in that case it must be a process that requires a time of the order of protein folding, about 1 psec. 

By geometry optimization using the CASSCF method, it was found that the geometry-optimized structure at a 90° rotation around the 11-bond gives a very different molecule from the cis form, which also does not fit into the cavity. As was customary at the time, the calculation was carried out in open space. To include the hindrance from the protein would require too much computational resources. 

Geometry optimization is no problem, but its purpose is just to find the structure corresponding to the energy minimum. It gives no information about the dynamics of the cis-trans isomerization in the protein. 

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