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Abstract 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.
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This content will become publicly available on December 1, 2026
Rhodopsin charge diffusion computations disclose contrasting color-tuning mechanisms
Our understanding of the rules controlling the spectral tuning of light absorbing proteins is limited. When looking at rhodopsins as canonical examples, the fact that the cavity incorporates the chromophore counterion in different positions and polar residues with different orientations, leads to patterns of electrostatic potential whose effect is not obvious. In this work we use a model of the optogenetic reporter Arch-3 capable to describe the effect of the diffusion of its counterion charge on both excitation energies (lambda-max) ) and chromophore geometry. By optimizing such charge for a set of increasing lambda values, we show that progression towards redder values occurs along two distinct paths featuring a “compact” or an “extended” charge diffusion respectively. These results are validated by showing that both paths replicate the experimentally observed relationships between lambda-max and chromophore isomerization in different sets of Arch-3 variants, NeoR variants and other microbial rhodopsins from 16 different organisms.
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- Award ID(s):
- 2102619
- PAR ID:
- 10647475
- Publisher / Repository:
- Nature Portfolio
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 16
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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