Insight into the isomerization mechanism of retinal proteins from hybrid quantum mechanics/molecular mechanics simulations

Sen, Saumik; Kar, Rup Kumar; Borin, Veniamin; Schapiro, Igor

doi:10.1002/wcms.1562

Cited by 18 publications

(10 citation statements)

References 115 publications

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“…These rearrangements in the retinal molecule at Δ t = 1 ps are compatible with an aborted ‘bicycle pedal’ mechanism of photoisomerization 14 , 47 – 50 in which the interactions of the C 19 methyl of retinal with specific residues in the tight binding pocket confer resistance to a larger rotation of this methyl group. The consequence for such aborted C 9 =C 10 isomerization is the release of energy over the polyene chain, affecting mostly C 8 and C 10 , which elbow in the opposite directions relative to the C 20 methyl (Fig.…”

Section: A Picosecond Light-induced Bent Retinalsupporting

confidence: 52%

Ultrafast structural changes direct the first molecular events of vision

Gruhl

Weinert

Rodrigues

et al. 2023

Nature

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Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs)1. A photon is absorbed by the 11-cis retinal chromophore of rhodopsin, which isomerizes within 200 femtoseconds to the all-trans conformation2, thereby initiating the cellular signal transduction processes that ultimately lead to vision. However, the intramolecular mechanism by which the photoactivated retinal induces the activation events inside rhodopsin remains experimentally unclear. Here we use ultrafast time-resolved crystallography at room temperature3 to determine how an isomerized twisted all-trans retinal stores the photon energy that is required to initiate the protein conformational changes associated with the formation of the G protein-binding signalling state. The distorted retinal at a 1-ps time delay after photoactivation has pulled away from half of its numerous interactions with its binding pocket, and the excess of the photon energy is released through an anisotropic protein breathing motion in the direction of the extracellular space. Notably, the very early structural motions in the protein side chains of rhodopsin appear in regions that are involved in later stages of the conserved class A GPCR activation mechanism. Our study sheds light on the earliest stages of vision in vertebrates and points to fundamental aspects of the molecular mechanisms of agonist-mediated GPCR activation.

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Section: A Picosecond Light-induced Bent Retinalsupporting

confidence: 52%

Ultrafast structural changes direct the first molecular events of vision

Gruhl

Weinert

Rodrigues

et al. 2023

Nature

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“…In the counterclockwise direction these two angles are -84° and +63°, respectively. This is reminiscent of the hula-twist isomerization mechanism 53,54 where these two adjacent bonds isomerize. Due to the concerted twist of two bonds, there is a disruption in the conjugation which leads to a charge redistribution between the C-and D-rings.…”

Section: Resultsmentioning

confidence: 95%

Photoisomerization of phytochrome chromophore models: An XMS-CASPT2 study

Rao

Schapiro

2022

Preprint

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Phytochromes are a superfamily of photoreceptors that harbor linear tetrapyrroles as chromophores. Upon light illumination, the linear tetrapyrrole chromophore undergoes a double bond isomerization which starts a photocycle. In this work, we studied the photoisomerization of chromophore models designed based on the C- and D-rings of the phycocyanobilin (PCB) chromophore. In total, five different models with varying substitutions were investigated. Firstly, the vertical excitation energies were benchmarked using different computational methods to establish the relative order of the excited states. Based on these calculations, we computed the photoisomerization profiles using the extended multi-state (XMS) version of the CASPT2 method. The profiles were obtained for both the clockwise and counterclockwise rotations of the C15=C16 bond in the Z and E isomers using a linear interpolation of internal coordinates between the Franck-Condon and MECI geometries. In the minimal chromophore model that lacks the substitutions at the pyrrole rings, the isomerization involves both C14-C15 and C15=C16 bonds of the methine bridge between the C- and D-rings, resembling the hula-twist motion. The MECIs are characterized by a partial charge transfer between the two pyrrole rings pointing towards a twisted intramolecular charge transfer. Systematic introduction of substituents leads to an increase in the steric repulsion between the two pyrrole rings causing a pretwist of the dihedral around the C15=C16 bond, which creates a preference for the counterclockwise isomerization. Upon introduction of the carbonyl group at the D-ring the charge transfer has increased. This changes the isomerization mechanism from hula-twist to one-bond flip.

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“…In the counterclockwise direction these two angles are À841 and +631, respectively. This is reminiscent of the hula-twist isomerization mechanism 54,55 where these two adjacent bonds isomerize. Due to the concerted twist of two bonds, there is a disruption in the conjugation which leads to a charge redistribution between the C-and D-rings.…”

Section: Photoisomerization Profiles At the Xms-caspt2 Levelmentioning

confidence: 99%