Tuning the Protein‐Induced Absorption Shifts of Retinal in Engineered Rhodopsin Mimics

Suomivuori, Carl‐Mikael; Lang, Lucas; Sundholm, Dage; Gámiz‐Hernández, Ana P.; Kaila, Ville R. I.

doi:10.1002/chem.201505126

Cited by 19 publications

(26 citation statements)

References 65 publications

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“…To overcome these limitations, recent theoretical studies have extended the quantum treatment to larger regions and suggested that at least one shell of amino acids in proximity of the RPSB chromophore participates in the photo-induced process. 20,24 These findings are qualitatively in line with earlier studies [26][27][28] on prototypical opsins by Elstner and coworkers, who found the environment to electrostatically respond to the photoexcitation of the chromophore when relaxed in a state-specific manner using either a quantum-in-quantum partition or through polarizable force fields. In all these cases, the observed effects were classified as "polarization" but is the polarization captured by a responsive (quantum or classical) treatment of the environment the same one re-covered in the quantum calculation of a large photoexcited region?…”

Section: Introductionsupporting

confidence: 90%

Electrostatic versus Resonance Interactions in Photoreceptor Proteins: The Case of Rhodopsin

Guareschi

Valsson

Curutchet

et al. 2016

J. Phys. Chem. Lett.

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Light sensing in photoreceptor proteins is subtly modulated by the multiple interactions between the chromophoric unit and its binding pocket. Many theoretical and experimental studies have tried to uncover the fundamental origin of these interactions but reached contradictory conclusions as to whether electrostatics, polarization, or intrinsically quantum effects prevail. Here, we select rhodopsin as a prototypical photoreceptor system to reveal the molecular mechanism underlying these interactions and regulating the spectral tuning. Combining a multireference perturbation method and density functional theory with a classical but atomistic and polarizable embedding scheme, we show that accounting for electrostatics only leads to a qualitatively wrong picture, while a responsive environment can successfully capture both the classical and quantum dominant effects. Several residues are found to tune the excitation by both differentially stabilizing ground and excited states and through nonclassical "inductive resonance" interactions. The results obtained with such a quantum-in-classical model are validated against both experimental data and fully quantum calculations.

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Section: Introductionsupporting

confidence: 90%

Electrostatic versus Resonance Interactions in Photoreceptor Proteins: The Case of Rhodopsin

Guareschi

Valsson

Curutchet

et al. 2016

J. Phys. Chem. Lett.

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“…The most extended color tuning study on a retinal protein was carried on the human cellular retinol binding protein II (hCRBPII) that was converted into a retinal binder 36 . Mutagenesis of the retinal-binding pocket lead to a protein with absorption at 644 nm 37 , 38 , a strong bathochromic shift that depends on the even distribution of the electrostatic potential across the entire polyene. However, one has to point out that hCRBPII is missing any RSBH + counterion and our data demonstrate that the situation is clearly different in NeoR with low importance of the binding pocket and a main contribution of the active site.…”

Section: Resultsmentioning

confidence: 99%

NeoR, a near-infrared absorbing rhodopsin

et al. 2020

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The Rhizoclosmatium globosum genome encodes three rhodopsin-guanylyl cyclases (RGCs), which are predicted to facilitate visual orientation of the fungal zoospores. Here, we show that RGC1 and RGC2 function as light-activated cyclases only upon heterodimerization with RGC3 (NeoR). RGC1/2 utilize conventional green or blue-light-sensitive rhodopsins (λmax = 550 and 480 nm, respectively), with short-lived signaling states, responsible for light-activation of the enzyme. The bistable NeoR is photoswitchable between a near-infrared-sensitive (NIR, λmax = 690 nm) highly fluorescent state (QF = 0.2) and a UV-sensitive non-fluorescent state, thereby modulating the activity by NIR pre-illumination. No other rhodopsin has been reported so far to be functional as a heterooligomer, or as having such a long wavelength absorption or high fluorescence yield. Site-specific mutagenesis and hybrid quantum mechanics/molecular mechanics simulations support the idea that the unusual photochemical properties result from the rigidity of the retinal chromophore and a unique counterion triad composed of two glutamic and one aspartic acids. These findings substantially expand our understanding of the natural potential and limitations of spectral tuning in rhodopsin photoreceptors.

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“…30,[79][80][81][82] Another commonly used approach is the second-order approximate coupled cluster singles and doubles model (CC2). 32,83 It has been assessed specifically for excitation energies of organic molecules. 84 However, excitation energy calculations using the methods described above are computationally too demanding for the "Large" QM region (Figure 1), considering the computation of 3000 snapshots from thermal sampling.…”

Section: Assessment Of the Electronic Structure Methodsmentioning

confidence: 99%

Structural Factors Determining the Absorption Spectrum of Channelrhodopsins: A Case Study of the Chimera C1C2

Adam

Wiebeler

Schapiro

2021

J. Chem. Theory Comput.

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Channelrhodopsins are photosensitive proteins that trigger flagella motion in single cell algae and have been successfully utilized in optogenetic applications. In optogenetics light is used to activate neural cells in living organisms, which can be achieved by exploiting the ion channel signaling of channelrhodopsins. Tailoring channelrhodopsins for such applications includes the tuning of the absorption maximum. In order to establish rational design and to obtain a desired spectral shift, a basic understanding of the absorption spectrum is required. We have studied the chimera C1C2 as a representative of this protein family and the first member with an available crystal structure. For this purpose, we sampled the conformations of C1C2 using QM/MM molecular dynamics, and subjected the resulting snapshots of the trajectory to excitation energy calculations using ADC(2) and simplified TD-DFT. In contrast to previous reports, we found that different hydrogen-bonding networks-involving the retinal protonated Schiff base, the putative counterions E162 and D292 as well as water molecules-had only a small impact on the absorption spectrum. However, in case of deprotonated E162 increasing the distance to the Schiff base hydrogen-bonding partner led to a systematic blue shift. The β-ionone ring rotation was identified as another important contributor. Yet the most important factor was found to be the bond length alternation and bond order alternation that were linearly correlated to the absorption maximum by up to 62 % and 82 %, respectively. We ascribe this novel insight into the structural basis of the absorption spectrum to our enhanced protein setup that includes membrane embedding as well as long and extensive sampling. File list (2) download file view on ChemRxiv manuscript_v1.30.pdf (1.81 MiB) download file view on ChemRxiv supplementary_v1.10.pdf (472.85 KiB)

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Tuning the Protein‐Induced Absorption Shifts of Retinal in Engineered Rhodopsin Mimics

Cited by 19 publications

References 65 publications

Electrostatic versus Resonance Interactions in Photoreceptor Proteins: The Case of Rhodopsin

Electrostatic versus Resonance Interactions in Photoreceptor Proteins: The Case of Rhodopsin

NeoR, a near-infrared absorbing rhodopsin

Structural Factors Determining the Absorption Spectrum of Channelrhodopsins: A Case Study of the Chimera C1C2

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