Toward An Understanding Of The Retinal Chromophore In Rhodopsin Mimics

Recently, a rhodopsin protein mimic was constructed by combining mutants of the cellular retinoic acid binding protein II (CRABPII) with an all-trans retinal chromophore. Here, we present a combine computational quantum mechanics/molecular mechanics (QM/MM) and experimental ultrafast kinetic study of CRABPII. We employ the QM/MM models to study the absorption (lambda(a)(max)), fluorescence (lambda(f)(max)), and reactivity of a CRABPII triple mutant incorporating the all-trans protonated chromophore (PSB-KLE-CRABPII). We also study the spectroscopy of the same mutant incorporating the unprotonated chromophore and of another double mutant incorporating the neutral unbound retinal molecule held inside the pocket. Finally, for PSB-KLE-CRABPII, stationary fluorescence spectroscopy and ultrafast transient absorption spectroscopy resolved two different evolving excited state populations which were computationally assigned to distinct locally excited and charge-transfer species. This last species is shown to evolve along reaction paths describing a facile isomerization of the biologically relevant 11-cis and 13-cis double bonds. This work represents a first exploratory attempt to model and study these artificial protein systems. It also indicates directions for improving the QM/MM models so that they could be more effectively used to assist the bottom-up design of genetically encodable probes and actuators employing the retinal chromophore

Effect of probe energy and competing pathways on time-resolved photoelectron spectroscopy signals: ring-opening reaction of 1,3-cyclohexadiene

The ring-opening dynamics of 1,3-cyclohexadiene (CHD) following UV excitation is studied using a model based on quantum molecular dynamics simulations with the ab-initio multiconfigurational Ehrenfest (AI-MCE) method coupled to the Dyson orbital approach for photoionisation cross sections. Time-dependent photoelectron spectra are calculated for probe photon energies in the range 2-15 eV. The calculations demonstrate the value of universal high-energy probes, capableof tracking the full photochemical dynamics of the molecule, as well as the benefit of more selective, lower-energy probes. The predicted signal, especially with the universal probes, becomes highly convoluted due to the contributions from multiple reaction paths, rendering interpretationdifficult unless complementary measurements and theoretical comparisons are available

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

Comparative modeling and ab initio multiconfigurational quantum chemistry are combined to investigate the reactivity of the human nonvisual photoreceptor melanopsin. It is found that both the thermal and photochemical isomerization of the 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 proposed by Warshel for visual pigments [Warshel A (1976) Nature 260(5553):679–683]. A comparison with the mechanisms documented for vertebrate (bovine) and invertebrate (squid) visual photoreceptors shows that such a mechanism is not affected by the diversity of the three chromophore cavities. Despite such invariance, trajectory computations indicate that although all receptors display less than 100 fs excited state dynamics, human melanopsin decays from the excited state ∼40 fs earlier than bovine rhodopsin. Some diversity is also found in the energy barriers controlling thermal isomerization. Human melanopsin features the highest computed barrier which appears to be ∼2.5 kcal mol(−1) higher than that of bovine rhodopsin. When assuming the validity of both the reaction speed/quantum yield correlation discussed by Warshel, Mathies and coworkers [Weiss RM, Warshel A (1979) J Am Chem Soc 101:6131–6133; Schoenlein RW, Peteanu LA, Mathies RA, Shank CV (1991) Science 254(5030):412–415] and of a relationship between thermal isomerization rate and thermal activation of the photocycle, melanopsin turns out to be a highly sensitive pigment consistent with the low number of melanopsin-containing cells found in the retina and with the extraretina location of melanopsin in nonmammalian vertebrates

Quantum–classical simulations of rhodopsin reveal excited-state population splitting and its effects on quantum efficiency

The activation of rhodopsin, the light-sensitive G-protein-coupled receptor responsible for dim-light vision in vertebrates, is driven by an ultrafast excited-state double-bond isomerization with a quantum efficiency of almost 70%. The origin of such light sensitivity is not understood and a key question is whether in-phase nuclear motion controls the quantum efficiency value. In this study we used hundreds of quantum–classical trajectories to show that, 15 fs after light absorption, a degeneracy between the reactive excited state and a neighbouring state causes the splitting of the rhodopsin population into subpopulations. These subpopulations propagate with different velocities and lead to distinct contributions to the quantum efficiency. We also show here that such splitting is modulated by protein electrostatics, thus linking amino acid sequence variations to quantum efficiency modulation. Finally, we discuss how such a linkage that in principle could be exploited to achieve higher quantum efficiencies would simultaneously increase the receptor thermal noise leading to a trade-off that may have played a role in rhodopsin evolution. [Figure not available: see fulltext.]

Quantum monte carlo treatment of the charge transfer and diradical electronic character in a retinal chromophore minimal model

The penta-2,4-dieniminium cation (PSB3) displays similar ground state and first excited state potential energy features as those of the retinal protonated Schiff base (RPSB) chromophore in rhodopsin. Recently, PSB3 has been used to benchmark several electronic structure methods, including highly correlated multireference wave function approaches, highlighting the necessity to accurately describe the electronic correlation in order to obtain reliable properties even along the ground state (thermal) isomerization paths. In this work, we apply two quantum Monte Carlo approaches, the variational Monte Carlo and the lattice regularized diffusion Monte Carlo, to study the energetics and electronic properties of PSB3 along representative minimum energy paths and scans related to its thermal cis-trans isomerization. Quantum Monte Carlo is used in combination with the Jastrow antisymmetrized geminal power ansatz, which guarantees an accurate and balanced description of the static electronic correlation thanks to the multiconfigurational nature of the antisymmetrized geminal power term, and of the dynamical correlation, due to the presence of the Jastrow factor explicitly depending on electron-electron distances. Along the two ground state isomerization minimum energy paths of PSB3, CASSCF calculations yield wave functions having either charge transfer or diradical character in proximity of the two transition state configurations. Here, we observe that at the quantum Monte Carlo level of theory, only the transition state with charge transfer character can be located. The conical intersection, which becomes highly sloped, is observed only if the path connecting the two original CASSCF transition states is extended beyond the diradical one, namely by increasing the bond-length-alternation (BLA). These findings are in good agreement with the results obtained by MRCISD+Q calculations, and they demonstrate the importance of having an accurate description of the static and dynamical correlation when studying isomerization and transition states of conjugated systems

Learning from photobiology how to design molecular devices using a computer

Learning how to model photo-responsive proteins may open the way to the design of lightpowered biomimetic molecular devices.</p

Cyclopropenone (c-C₃H₂O) as a Tracer of the nonequilibrium chemistry mediated by galactic cosmic rays in interstellar ices

While gas-phase astrochemical reaction networks nicely replicate the abundance of hydrogen-deficient organics like linear cyanopolyynes, pathways to complex organic molecules (COMs)—organic molecules with six or more atoms—have not been completely understood, with gas-phase models often significantly underestimating fractional abundances of the astronomically observed organics by orders of magnitude. Here, by exploiting cyclopropenone (c-C3H2O) as a tracer, laboratory experiments on the processing of an ice mixture of acetylene(C2H2) and carbon monoxide (CO) by energetic electrons coupled with astrochemical model simulations expose a previously poorly explored reaction class leading to COMs via galactic cosmic-ray-mediated nonequilibrium chemistry. These processes occur within interstellar ices at ultralow temperatures, but not through traditional radical–radical pathways on grain surfaces in the warm-up phase of the ices as hypothesized for the last decades, but more likely through barrierless excited state reactions during the irradiation

Probing the Electronic Structure of Bulk Water at the Molecular Length Scale with Angle-Resolved Photoelectron Spectroscopy

We report a combined experimental and theoretical study of bulk water photoionization. Angular distributions of photoelectrons produced by ionizing the valence bands of neat water using X-ray radiation (250–750 eV) show a limited (∼20%) decrease in the β anisotropy parameter compared to the gas phase, indicating that the electronic structure of the individual water molecules can be probed. We show that, in the high-energy regime, photoionization of bulk can be described using an incoherent superposition of individual molecules, in contrast to a low-energy regime where photoionization probes delocalized entangled states of molecular aggregates. The two regimes—low versus high energy—are limiting cases where the de Broglie wavelength of the photoelectron is larger or smaller than the intermolecular distance between water molecules, respectively. The comparison of measured and computed anisotropies reveals that the reduction in β at high kinetic energies is mostly due to scattering rather than rehybridization due to solvation