Ultrafast processes in light-absorbing proteins have been implicated in the primary step in the light-to-energy conversion and the initialization of photoresponsive biological functions. Theory and ...computations have played an instrumental role in understanding the molecular mechanism of such processes, as they provide a molecular-level insight of structural and electronic changes at ultrafast time scales that often are very difficult or impossible to obtain from experiments alone. Among theoretical strategies, the application of hybrid quantum mechanics and molecular mechanics (QM/MM) models is an important approach that has reached an evident degree of maturity, resulting in several important contributions to the field. This review presents an overview of state-of-the-art computational studies on subnanosecond events in rhodopsins, photoactive yellow proteins, phytochromes, and some other photoresponsive proteins where photoinduced double-bond isomerization occurs. The review also discusses current limitations that need to be solved in future developments.
In the past, the design of light-driven single molecule rotary motors has been mainly guided by the modification of their ground-state conformational properties. Further progress in this field is ...thus likely to be achieved through a detailed understanding of light-induced dynamics of the system and the ways of modulating it by introducing chemical modifications. In the present theoretical work, the analysis of model organic chromophores and synthesized rotary motors is used for rationalizing the effect of electron-withdrawing heteroatoms (such as a cationic nitrogen) on the topography and branching plane of mechanistically relevant conical intersections. Such an analysis reveals how the character of rotary motion could be changed from a precessional motion to an axial rotational motion. These concepts are then used to design and build quantum chemical models of three distinct types of Schiff base rotary motors. One of these models, featuring the synthetically viable indanylidenepyrroline framework, has conical intersection structures consistent with an axial rotation not hindered by ground-state conformational barriers. It is expected that this type of motor should be capable of funneling the photon energy into specific rotary modes, thus achieving photoisomerization quantum efficiencies comparable to those seen in visual pigments.
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.
Microbial rhodopsins are photoreceptive membrane proteins that transport various ions using light energy. While they are widely used in optogenetics to optically control neuronal activity, rhodopsins ...that function with longer-wavelength light are highly demanded because of their low phototoxicity and high tissue penetration. Here, we achieve a 40-nm red-shift in the absorption wavelength of a sodium-pump rhodopsin (KR2) by altering dipole moment of residues around the retinal chromophore (KR2 P219T/S254A) without impairing its ion-transport activity. Structural differences in the chromophore of the red-shifted protein from that of the wildtype are observed by Fourier transform infrared spectroscopy. QM/MM models generated with an automated protocol show that the changes in the electrostatic interaction between protein and chromophore induced by the amino-acid replacements, lowered the energy gap between the ground and the first electronically excited state. Based on these insights, a natural sodium pump with red-shifted absorption is identified from Jannaschia seosinensis.
We use quantum-classical trajectories to investigate the origin of the different photoisomerization quantum efficiency observed in the dim-light visual pigment Rhodopsin and in the light-driven ...biomimetic molecular rotor para-methoxy N-methyl indanylidene-pyrrolinium (MeO-NAIP) in methanol. Our results reveal that effective light-energy conversion requires, in general, an auxiliary molecular vibration (called promoter) that does not correspond to the rotary motion but synchronizes with it at specific times. They also reveal that Nature has designed Rhodopsin to exploit two mechanisms working in a vibrationally coherent regime. The first uses a wag promoter to ensure that ca. 75% of the absorbed photons lead to unidirectional rotations. The second mechanism ensures that the same process is fast enough to avoid directional randomization. It is found that MeO-NAIP in methanol is incapable of exploiting the above mechanisms resulting into a 50% quantum efficiency loss. However, when the solvent is removed, MeO-NAIP rotation is predicted to synchronize with a ring-inversion promoter leading to a 30% increase in quantum efficiency and, therefore, biomimetic behavior.
Spontaneous electrical signals in the retina's photoreceptors impose a limit on visual sensitivity. Their origin is attributed to a thermal, rather than photochemical, activation of the transduction ...cascade. Although the mechanism of such a process is under debate, the observation of a relationship between the maximum absorption wavelength (λ max ) and the thermal activation kinetic constant (k) of different visual pigments (the Barlow correlation) indicates that the thermal and photochemical activations are related. Here we show that a quantum chemical model of the bovine rod pigment provides a molecular-level understanding of the Barlow correlation. The transition state mediating thermal activation has the same electronic structure as the photoreceptor excited state, thus creating a direct link between λ max and k. Such a link appears to be the manifestation of intrinsic chromophore features associated with the existence of a conical intersection between its ground and excited states.
The understanding of how the rhodopsin sequence can be modified to exactly modulate the spectroscopic properties of its retinal chromophore, is a prerequisite for the rational design of more ...effective optogenetic tools. One key problem is that of establishing the rules to be satisfied for achieving highly fluorescent rhodopsins with a near infrared absorption. In the present paper we use multi-configurational quantum chemistry to construct a computer model of a recently discovered natural rhodopsin, Neorhodopsin, displaying exactly such properties. We show that the model, that successfully replicates the relevant experimental observables, unveils a geometrical and electronic structure of the chromophore featuring a highly diffuse charge distribution along its conjugated chain. The same model reveals that a charge confinement process occurring along the chromophore excited state isomerization coordinate, is the primary cause of the observed fluorescence enhancement.
Spectral data show that the photoisomerization of retinal protonated Schiff base (rPSB) chromophores occurs on a 100 fs time scale or less in vertebrate rhodopsins, it is several times slower in ...microbial rhodopsins and it is between one and 2 orders of magnitude slower in solution. These time scale variations have been attributed to specific modifications of the topography of the first excited state potential energy surface of the chromophore. However, it is presently not clear which specific environment effects (e.g., electrostatic, electronic, or steric) are responsible for changing the surface topography. Here, we use QM/MM models and excited state trajectory computations to provide evidence for an increase in electronic mixing between the first and the second excited state of the chromophore when going from vertebrate rhodopsin to the solution environments. Ultimately, we argue that a correlation between the lifetime of the first excited state and electronic mixing between such state and its higher neighbor, may have been exploited to evolve rhodopsins toward faster isomerization and, possibly, light-sensitivity.
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