Mode-Specific Photoresponse\nof Retinal Protonated\nSchiff Base Isomers in the Reversible Photochromic Reactions of Microbial\nand Animal Rhodopsins

The primary photoisomerization reactions of the all-<i>trans</i> to 13-<i>cis</i> and 11-<i>cis</i> to all-<i>trans</i> retinal protonated Schiff base (RPSB)\nin microbial\nand animal rhodopsins, respectively, occur on a subpicosecond time\nscale with high quantum yields. At the same time, the isolated RPSB\nexhibits slower excited-state decay, in particular, in its all-<i>trans</i> form, and hence the interaction with the protein environment\nis capable of changing the time scale as well as the specificity of\nthe reaction. Here, by using the high-level QM/MM calculations, we\nprovide a comparative study of the primary photoresponse of <i>cis</i> and <i>trans</i> RPSB isomers in both the\ninitial forms and first photoproducts of microbial Krokinobacter eikastus rhodopsin 2 (KR2) and Halobacterium salinarum bacteriorhodopsin (BR), and\nanimal Bos taurus visual rhodopsin\n(Rho). By simulating photoabsorption band shapes of RPSB inside the\nproteins, we show that its photoresponse is highly mode-specific for\nthe forward reactions, resulting in excitation of those vibrational\nmodes that facilitate particular double-bond isomerization. The reverse\nreaction shows specificity only for 13-<i>cis</i> isomers\nin microbial rhodopsins, whereas the specificity is lost for all-<i>trans</i> RPSB in visual rhodopsin. This indicates evolutionary\nhighly tuned 11-<i>cis</i> chromophore–protein interactions\nin visual rhodopsin. We also highlight the differences in the photoresponse\nof RPSB in two microbial rhodopsins and discuss the implications to\ntheir excited-state dynamics.