Ground-state properties of the retinal molecule: from quantum mechanical to classical mechanical computations of retinal proteins

Bondar, Ana‐Nicoleta; Knapp-Mohammady, Michaela; Suhai, Sándor; Fischer, Stefan; Smith, Jeremy C.

doi:10.1007/s00214-011-1054-1

Cited by 16 publications

(26 citation statements)

References 98 publications

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“…A similar conclusion is reached by a recent theoretical work [28]. The standard CCD cleavage reaction mechanism [9,[29][30][31][32] is supposed to proceed through a dioxetaneinvolving variant as the more likely route [33]. This correlates with theoretical calculations of dioxygenase reaction profiles [31].…”

Section: Resultssupporting

confidence: 86%

“…This involves a simple rotation of the substituents around the C 12 -C 13 bond. The standard CCD cleavage reaction mechanism [9,[29][30][31][32] is supposed to proceed through a dioxetaneinvolving variant as the more likely route [33]. They conclude that it is relatively low and state that 'when bound to the protein opsin to form rhodopsin, retinal could have either conformation about the 12-13 bond'.…”

Section: Resultsmentioning

confidence: 99%

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Insights into the formation of carlactone from in‐depth analysis of theCCD8‐catalyzed reactions

et al. 2017

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Strigolactones are a new class of phytohormones synthesized from carotenoids via carlactone. The complex structure of carlactone is not easily deducible from its precursor, a cis-configured β-carotene cleavage product, and is thus formed via a poorly understood series of reactions and molecular rearrangements, all catalyzed by only one enzyme, the carotenoid cleavage dioxygenase 8 (CCD8). Moreover, the reactions leading to carlactone are expected to form a second, yet unidentified product. In this study, we used C and O-labeling to shed light on the reactions catalyzed by CCD8. The characterization of the resulting carlactone by LC-MS and NMR, and the identification of the assumed, less accessible second product allowed us to formulate a minimal reaction mechanism for carlactone generation.

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Insights into the formation of carlactone from in‐depth analysis of theCCD8‐catalyzed reactions

et al. 2017

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“…Several different force fields have been developed for the ground state retinal and reviewed in a sophisticated study by Bondar et al . Since the current study involves retinal SB with different protonation states, we chose the parameter set released in the CHARMM36 all‐atom force field, which provides parameters for both protonation states of the retinal SB and is consistent with the force field used for the protein and lipids.…”

Section: Resultsmentioning

confidence: 99%

“…To investigate the role of retinal isomerization in pathway connectivity, hypothetical states (bR-like, M1-like and O-like) were generated by varying the isomeric state of the retinal C13 5 C14 bond for each protonation state. Several different force fields have been developed for the ground state retinal 60-62 and reviewed in a sophisticated study by Bondar et al 63 Since the current study involves retinal SB with different protonation states, we chose the parameter set released in the CHARMM36 all-atom force field, which provides parameters for both protonation states of the retinal SB and is consistent with the force field used for the protein and lipids. This parameter set (not published) was developed in the same manner as CHARMM General Force Field for drug-like molecules.…”

Section: Resultsmentioning

confidence: 99%

Unraveling the mechanism of proton translocation in the extracellular half‐channel of bacteriorhodopsin

Gunner

2016

Proteins

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Bacteriorhodopsin, a light activated protein that creates a proton gradient in halobacteria, has long served as a simple model of proton pumps. Within bacteriorhodopsin, several key sites undergo protonation changes during the photocycle, moving protons from the higher pH cytoplasm to the lower pH extracellular side. The mechanism underlying the long-range proton translocation between the central (the retinal Schiff base SB216, D85, and D212) and exit clusters (E194 and E204) remains elusive. To obtain a dynamic view of the key factors controlling proton translocation, a systematic study using molecular dynamics simulation was performed for eight bacteriorhodopsin models varying in retinal isomer and protonation states of the SB216, D85, D212, and E204. The side-chain orientation of R82 is determined primarily by the protonation states of the residues in the EC. The side-chain reorientation of R82 modulates the hydrogen-bond network and consequently possible pathways of proton transfer. Quantum mechanical intrinsic reaction coordinate calculations of proton-transfer in the methyl guanidinium-hydronium-hydroxide model system show that proton transfer via a guanidinium group requires an initial geometry permitting proton donation and acceptance by the same amine. In all the bacteriorhodopsin models, R82 can form proton wires with both the CC and the EC connected by the same amine. Alternatively, rare proton wires for proton transfer from the CC to the EC without involving R82 were found in an O' state where the proton on D85 is transferred to D212.

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“…The GROMOS96 43a2 force field parameters were utilized for the protein and the Berger lipid parameters were used for the lipid component of the membrane protein82. The SPC water model was used for hydration and the ground-state retinal parameters83 for both the 11- cis and all-trans retinal chromophore were obtained from the Bondar group.…”

Section: Methodsmentioning

confidence: 99%

Vibrational resonance, allostery, and activation in rhodopsin-like G protein-coupled receptors

Woods

Dutta

Klein‐Seetharaman

2016

Sci Rep

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G protein-coupled receptors are a large family of membrane proteins activated by a variety of structurally diverse ligands making them highly adaptable signaling molecules. Despite recent advances in the structural biology of this protein family, the mechanism by which ligands induce allosteric changes in protein structure and dynamics for its signaling function remains a mystery. Here, we propose the use of terahertz spectroscopy combined with molecular dynamics simulation and protein evolutionary network modeling to address the mechanism of activation by directly probing the concerted fluctuations of retinal ligand and transmembrane helices in rhodopsin. This approach allows us to examine the role of conformational heterogeneity in the selection and stabilization of specific signaling pathways in the photo-activation of the receptor. We demonstrate that ligand-induced shifts in the conformational equilibrium prompt vibrational resonances in the protein structure that link the dynamics of conserved interactions with fluctuations of the active-state ligand. The connection of vibrational modes creates an allosteric association of coupled fluctuations that forms a coherent signaling pathway from the receptor ligand-binding pocket to the G-protein activation region. Our evolutionary analysis of rhodopsin-like GPCRs suggest that specific allosteric sites play a pivotal role in activating structural fluctuations that allosterically modulate functional signals.

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Ground-state properties of the retinal molecule: from quantum mechanical to classical mechanical computations of retinal proteins

Cited by 16 publications

References 98 publications

Insights into the formation of carlactone from in‐depth analysis of theCCD8‐catalyzed reactions

Insights into the formation of carlactone from in‐depth analysis of theCCD8‐catalyzed reactions

Unraveling the mechanism of proton translocation in the extracellular half‐channel of bacteriorhodopsin

Vibrational resonance, allostery, and activation in rhodopsin-like G protein-coupled receptors

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