Tracking the excited-state time evolution of the visual pigment with multiconfigurational quantum chemistry

Abstract

The primary event that initiates vision is the photoinduced isomerization of retinal in the visual pigment rhodopsin (Rh). Here, we use a scaled quantum mechanics/molecular mechanics potential that reproduces the isomerization path determined with multiconfigurational perturbation theory to follow the excited-state evolution of bovine Rh. The analysis of a 140-fs trajectory provides a description of the electronic and geometrical changes that prepare the system for decay to the ground state. The data uncover a complex change of the retinal backbone that, at Ϸ60-fs delay, initiates a space saving ''asynchronous bicycle-pedal or crankshaft'' motion, leading to a conical intersection on a 110-fs time scale. It is shown that the twisted structure achieved at decay features a momentum that provides a natural route toward the photoRh structure recently resolved by using femtosecond-stimulated Raman spectroscopy.photoisomerization ͉ rhodopsin ͉ vision T he visual pigment rhodopsin (Rh) (1, 2) is a G protein-coupled receptor containing a 11-cis retinal chromophore (PSB11) bounded to a lysine residue (Lys-296) via a protonated Schiff base linkage (see Fig. 1). While the biological activity of Rh is triggered by the light-induced 11-cis all-trans isomerization of PSB11, this reaction owes its efficiency (e.g., short time scale and high quantum yields) to the protein cavity (1). Recently, the mechanism of the isomerization of retinal in Rh has been investigated by using femtosecond-stimulated Raman spectroscopy (FSRS) (3). Kukura et al. (3) have reported on experimentally derived structures of photoRh and bathoRh, namely the first and second ground-state intermediates of the Rh photocycle.While such progress has provided information on the structural changes achieved 200 fs after light absorption, the faster structural changes prompting the excited-state decay of PSB11 (i.e., the central event of the isomerization mechanism) remain to be established. Indeed, it has been suggested that such decay may occur on a 60-fs time scale through fast hydrogen out-ofplane (HOOP) motion (3), whereas the traditional view points to a slower Ϸ150-fs decay driven by cis-trans isomerization motion (4). In principle, molecular dynamics simulations featuring a quantum chemical description of the chromophore can be used to address such issues. This fact was shown by Warshel (5) using semiempirical quantum chemistry to describe PSB11 and geometrical constraints to account for the protein environment. Later, Birge and Hubbard (6) reported a different semiempirical study of an explicit chromophore-counterion pair evolving along a single coordinate. While the first simulation of the retinal photoisomerization using a full atomic-level protein model (7) was reported for the related receptor bacterio-Rh (bR), attempts to simulate the PSB11 excited-state motion in a complete Rh model are more recent (8-10). On the other hand, a quantitative evaluation of the isomerization coordinate and time scale requires, as a prerequisite, an accurate excited-st...

Functional electric field changes in photoactivated proteins revealed by ultrafast Stark spectroscopy of the Trp residues

“…Retinal and retinal proteins show a large dipole moment increase already in the Franck-Condon region, which has been measured by Stark spectroscopy (26,27) and must induce an instantaneous rise of the signal discussed here. In addition to that, a twist-induced charge translocation (28) is predicted to increase dramatically the retinal dipole moment on a sub-20-fs timescale when the molecule reaches the conical intersection (29). This 100-fs delayed event should induce further rise of the signal, but no such contribution is observed here.…”

Product formation in rhodopsin by fast hydrogen motions

“…4 This photoreaction has been studied in the past both in vacuo 5-7 and in the protein binding pocket. [8][9][10][11][12] All calculations support an ultrafast dynamics through a conical intersection (CI), which directly connects the excited and ground state potentials of the retinal chromophore.Very recent hybrid QM(CASSCF)/MM simulations in Rh 13 have produced experimentally accurate transient sub-20 fs spectroscopies of the CI dynamics and primary visual event (i.e., the 200 fs photorhodopsin formation) that are supportive of a space saving photoisomerization mechanism reminiscent of Warshel's bicycle pedal model. 14 These findings alone, however, can not explain why the photoisomerization in rhodopsin is so uniquely efficient.…”

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

“…1B) passing through a conical intersection (CI). Such a path has been located along the S 1 potential energy surface by constructing a multiconfigurational quantum chemistry (MCQC) based computer model of the photoreceptor (29)(30)(31) and spectroscopically supported by probing in the infrared (31). More recently (32), the same computer model has been used to map the Rh thermal isomerization path (Fig.…”