Prediction of structural and environmental effects on the S1S0 energy gap and jump probability in double-bond cis—trans photoisomeriz

131

204

We demonstrate that ''brute force'' quantum-mechanics͞molecu-lar-mechanics computations based on ab initio (i.e., first principles) multiconfigurational perturbation theory can reproduce the absorption maxima of a set of modified bovine rhodopsins with an accuracy allowing for the analysis of the factors determining their colors. In particular, we show that the theory accounts for the changes in excitation energy even when the proteins display the same charge distribution. Three color-tuning mechanisms, leading to changes of close magnitude, are demonstrated to operate in these conditions. The first is based on the change of the conformation of the conjugated backbone of the retinal chromophore. The second operates through the control of the distance between the positive charge residing on the chromophore and the carboxylate counterion. Finally, the third mechanism operates through the changes in orientation of the chromophore relative to the protein. These results offer perspectives for the unbiased computational design of mutants or chemically modified proteins with wanted optical properties.excited states ͉ quantum mechanics͞molecular mechanics R ecently, protein mutants displaying properties such as high binding affinities and novel catalytic activities (1, 2) have been designed by using computational methods based on molecular mechanics. In a close context, substrate selectivity has been simulated by using more advanced tools based on density functional theory and molecular mechanics paving the way to the design of mutations that convert receptors into enzymes (3). However, the design of mutants with specific spectral properties, such as color and luminescence, represents a more complex problem. In these cases, the quantum chemical method used must be capable to describe both ground and electronically excited states of the protein chromophore. The ab initio (i.e., first-principles) complete-active-space self-consistent-field (CASSCF) method (4) is a multiconfigurational method offering maximum flexibility for an unbiased description of the electronic and equilibrium structure of a molecule (i.e., with no empirically derived parameters and avoiding single-reference wavefunctions). Furthermore, the CASSCF wave function can be used for subsequent multiconfigurational second-order perturbation theory (5) computations (CASPT2) of the dynamic correlation energy of each state ultimately leading to a nearly quantitative evaluation of the excitation energies of organic compounds (6, 7). The CASPT2 ability to describe exotic bonding has been recently assessed (8).In a previous study (9), we implemented the ab initio CASPT2͞͞CASSCF protocol (where equilibrium geometries and electronic energies are determined at the CASSCF and CASPT2 levels, respectively) in a quantum mechanics͞ molecular mechanics (QM͞MM) scheme (10-12) allowing for the evaluation of the excitation energy of chromophores (treated quantum mechanically) embedded in a protein environment (described by a MM force field).The absorption and fluorescence max...

Section: Resultssupporting

confidence: 61%

The color of rhodopsins at theab initiomulticonfigurational perturbation theory resolution

Coto

Strambi

Ferré

et al. 2006

131

204

“…As a prerequisite for the interpretation of our data we recall that in Rh (26) the S 1 state of PSB11 has a dominant charge transfer character as originally proposed by Michl, BonacicKoutecky, and coworkers (27,28). Upon S 0 3 S 1 excitation, the positive charge, initially located on the -NAC15-moiety, moves away along the -skeleton, leading to the observed large values of ⌬ and f. The charge distributions of the S 0 and S 1 states reflect the different nature of the corresponding wavefunctions that, with respect to the C11AC12 bond, can be associated with resonance formula displaying a charge in the -NAC15-half or ␤-ionone half of the retinal backbone.…”

Section: Resultssupporting

confidence: 54%

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

Frutos

Andruniów²,

Santoro³

et al. 2007

272

420

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...

“…It is established (25) that, in vacuo, the S 1 state of PSB11 has a dominant hole-pair (ionic) character as originally proposed by Michl and coworkers (28,29). Indeed, upon S 0 3 S 1 excitation, approximately half of the positive charge initially located on the -N ϭ C 15 -moiety moves away along the -skeleton, leading to large values of ⌬ and f. In contrast, the S 2 state has a dominant dot-dot (covalent) character, the charge remains on -N ϭ C 15 -, leading to low ⌬ and f values for the S 0 3 S 2 transition.…”

Section: Resultsmentioning

confidence: 83%

Structure, initial excited-state relaxation, and energy storage of rhodopsin resolved at the multiconfigurational perturbation theory level

Andruniów

Ferré²,

Olivucci³

2004

238

343

We demonstrate that a ''brute force'' quantum chemical calculation based on an ab initio multiconfigurational second order perturbation theory approach implemented in a quantum mechanics͞ molecular mechanics strategy can be applied to the investigation of the excited state of the visual pigment rhodopsin (Rh) with a computational error <5 kcal⅐mol ؊1 . As a consequence, the simulation of the absorption and fluorescence of Rh and its retinal chromophore in solution allows for a nearly quantitative analysis of the factors determining the properties of the protein environment. More specifically, we demonstrate that the Rh environment is more similar to the ''gas phase'' than to the solution environment and that the so-called ''opsin shift'' originates from the inability of the solvent to effectively ''shield'' the chromophore from its counterion. The same strategy is used to investigate three transient structures involved in the photoisomerization of Rh under the assumption that the protein cavity does not change shape during the reaction. Accordingly, the analysis of the initially relaxed excited-state structure, the conical intersection driving the excitedstate decay, and the primary isolable bathorhodopsin intermediate supports a mechanism where the photoisomerization coordinate involves a ''motion'' reminiscent of the so-called bicycle-pedal reaction coordinate. Most importantly, it is shown that the mechanism of the Ϸ30 kcal⅐mol ؊1 photon energy storage observed for Rh is not consistent with a model based exclusively on the change of the electrostatic interaction of the chromophore with the protein͞counterion environment.photoisomerization ͉ quantum mechanics ͉ molecular mechanics ͉ retinal ͉ vision T he visual pigment rhodopsin (Rh) (1, 2) is a G proteincoupled receptor containing an 11-cis retinal chromophore (PSB11) bounded to a lysine residue (Lys-296) via a protonated Schiff base linkage (see Scheme 1). While the biological activity of Rh is triggered by the light-induced 11-cis 3 all-trans isomerization of PSB11, this reaction owes its efficiency (e.g., short time scale and quantum yields) to the protein cavity (1). Accordingly, investigation of the environment-dependent properties of PSB11 is a prerequisite for understanding the Rh ''catalytic'' effect. The equilibrium geometry, absorption maxima ( max a ), and fluorescence maxima ( max f ) are indicators of the environment effect. In fact, whereas the geometry of PSB11 is nearly planar in a crystal (3), in bovine Rh it has a helical conformation (4). Similarly, the 445-nm max a observed for PSB11 in methanol (5) is red-shifted to 498 nm in Rh (1, 2): an effect known as the opsin shift.The Rh fluorescence band ranges from 530 to 780 nm (6). The max f has been reported (6) to be excitation wavelength-dependent, shifting from 595 to 704 nm when the excitation wavelength is shifted from 472 to 568 nm. This observation is consistent with the idea that the emission arises from a nonstationary unrelaxed excited-state population. In methanol solution the PSB11...