Comparative modeling and ab initio multiconfigurational quantum chemistry are combined to investigate the reactivity of the human non-visual photoreceptor melanopsin. It is found that both the thermal and photochemical isomerization of melanopsin 11-cis retinal chromophore occur via a space-saving mechanism involving the unidirectional, counterclockwise twisting of the =C11H-C12H= moiety with respect to its Lys340-linked frame as first proposed by Warshel. A comparison with the mechanisms documented for vertebrate (bovine) and invertebrate (squid) visual photoreceptors shows that such mechanism is not affected by the diversity of the three chromophore cavities. In spite of such invariance, trajectory computations indicate that while all receptors display less than 100 fs excited state dynamics, human melanopsin decays from the excited state ca. 40 fs earlier than bovine rhodopsin. A significant diversity is also found in the energy barriers controlling thermal isomerization. Human melanopsin features the highest computed barrier which appears to be higher than that of bovine rhodopsin. When assuming the validity of the reaction speed/quantum yield correlation proposed by Mathies and coworkers and of the relationship between thermal isomerization rate and photocycle activation originally proposed by Barlow, melanopsin turns out to be a highly sensitive pigment consistently with the low number of melanopsin-containing cells found in the retina and with the extra-retina deep brain location of melanopsin in non-mammalian vertebrates.

Comparison of the isomerization mechanisms of human melanopsin and invertebrate and vertebrate rhodopsins

247th National Meeting (2014)

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