Rhodopsins are photoactive proteins that catalyze various physicochemical reactions in microbial and animal cells that underlie different biological functions, such as vision, pumping specific ions into or out of the cell, phototaxis. The primary photochemical reaction in rhodopsins is isomerization of the chromophore, the protonated Schiff base retinal (PSBR). Microbial rhodopsins contain trans retinal, which isomerizes to the 13-cis form. In contrast, animal rhodopsins contain 11-cis retinal, which undergoes isomerization to the trans form.A high isomerization rate within hundreds of femtoseconds in various rhodopsins is provided in different ways. Based on our previous calculations , we conclude that the visual photoreceptors rely on the ultrafast intrinsic photoresponse of their 11-cis chromophore, whereas bacterial rhodopsins tune the photoresponse of the all-trans RPSB chromophore by particularly reducing the barrier height about the C13 = C14 double bond.The protein environment also plays an important role in providing high quantum yield and specificity of retinal isomerization.
Here, we aim at revealing the catalytic role played by the protein in the primary photochemical reaction, which results in the retinal isomerization about a specific double bond in various protein environments. By using high-level extended multi-configuration quasi-degenerate perturbation theory (XMCQDPT2) combined with the effective fragment potential (EFP) method, we model photoabsorption profiles of PSBR inside the retinal-binding pockets of microbial rhodopsin KR2 and visual rhodopsin and compare them with those obtained for the chromophore in the gas phase. By analyzing vibronic band shapes, we explore the early-time excited-state dynamics of PSBR and show that the protein environment alters vibrational modes that are active upon the S0-S1 transition, facilitating specific photoisomerization. Based on molecular dynamics sampling, we also study structural inhomogeneity and flexibility of the retinal-binding sites of rhodopsins. We show that through formation of a strong hydrogen bond between the retinal Schiff base and the counterion, the PSBR conformation can be changed. This results in pre-twisting of the specific double bond in the ground state, which enhances the activity of both the localized stretching and hydrogen-out-of-plane (HOOP) modes upon photoexcitation. This allows us to show, for the first time, a direct link between the structure of the retinal-binding pocket and the reaction dynamics of PSBR in the proteins.
This work is supported by the Russian Foundation for Basic Research (grant no. 19-33-90254). The research is carried out using the equipment of the shared research facilities of HPC computing resources at Lomonosov Moscow State University as well as the local resources provided through the Lomonosov Moscow State University Program of Development.