QM/MM Study of the Structure, Energy Storage, and Origin of the Bathochromic Shift in Vertebrate and Invertebrate Bathorhodopsins

Sekharan, Sivakumar; Morokuma, Keiji

doi:10.1021/ja200322w

Cited by 38 publications

(64 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…for studying related retinal proteins (21)(22)(23)(24)(25)(26)(27). The isomerization energy, i.e., the energy of the TS when all H-bonds are intact, was calculated to be 40 kcal/mol, which increases to 106 kcal/mol on disrupting the H-bonds in the TS.…”

Section: Resultsmentioning

confidence: 99%

Unusual kinetics of thermal decay of dim-light photoreceptors in vertebrate vision

Guo

Sekharan

Liu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

We present measurements of rate constants for thermal-induced reactions of the 11-cis retinyl chromophore in vertebrate visual pigment rhodopsin, a process that produces noise and limits the sensitivity of vision in dim light. At temperatures of 52.0-64.6°C, the rate constants fit well to an Arrhenius straight line with, however, an unexpectedly large activation energy of 114 ± 8 kcal/mol, which is much larger than the 60-kcal/mol photoactivation energy at 500 nm. Moreover, we obtain an unprecedentedly large prefactor of 10 72±5 s −1 , which is roughly 60 orders of magnitude larger than typical frequencies of molecular motions! At lower temperatures, the measured Arrhenius parameters become more normal: E a = 22 ± 2 kcal/mol and A pref = 10 9±1 s −1 in the range of 37.0-44.5°C. We present a theoretical framework and supporting calculations that attribute this unusual temperature-dependent kinetics of rhodopsin to a lowering of the reaction barrier at higher temperatures due to entropy-driven partial breakup of the rigid hydrogen-bonding network that hinders the reaction at lower temperatures.non-Arrhenius | dim-light vision | transition state theory | isomerization rate R hodopsin is a vertebrate dim-light photoreceptor. Molecular studies of rhodopsin in recent decades have largely focused on its photochemistry and photoactivation (1-3). However, complete understanding of rhodopsin's function requires characterization of its thermal properties because thermal isomerization of the 11-cis retinyl chromophore can trigger the same physiological response as photo-isomerization, generating false visual signals as dark noise that jeopardizes photosensitivity (4-6). To enhance dim-light vision, rhodopsin has evolved to acquire remarkable thermal stability with a half-life of 420 y as determined by electrophysiological experiments using the outer segments of rod cells at 36°C (4). However, the molecular mechanism for the thermal stability has remained unclear. Here, we have addressed this by exploring the temperature dependence of thermal decay rate constants k(T) associated with isomerization of the retinyl chromophore and hydrolysis of the chromophore protonated Schiff-base (PSB) linkage, for temperatures ranging from the physiological temperature of 37.0°C to 64.6°C. In the upper range of temperatures from 52.0°C to 64.6°C, we find that the rate constants determined by UV-visible spectroscopy follow a linear Arrhenius model, k(T) = A pref exp(−E a /k B T), where k B is the Boltzmann constant (Fig. 1A). The slope, however, is very steep, giving an elevated activation energy, E a = 114 ± 8 kcal/mol. Surprisingly, this value is much higher than the photoactivation energy at visible wavelengths (60 kcal/mol at 500 nm). E a is also much higher than the reaction enthalpy change (32-35 kcal/mol) (7, 8) (Fig. 1B). In the lower temperature range of our rate constant measurements, 37.0-44.5°C, the slope of the Arrhenius plot decreases abruptly, as shown in Fig. 1A. Fitting a straight line through the low temperature points prod...

show abstract

Section: Resultsmentioning

confidence: 99%

Unusual kinetics of thermal decay of dim-light photoreceptors in vertebrate vision

Guo

Sekharan

Liu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…80 Blomgren and Larsson used the ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) CASSCF/AMBER type of calculations to obtain a stored energy of 22.4 kcal mol À1 . 84 Such a significant difference between the value of photon energy storage found by Gascon and Batista 84 and by other authors, 34,45,46,80,82,83 including the authors of this paper, may be due to the employment of different rhodopsin/bathorhodopsin structural models in QM/MM calculations. Molecular dynamics calculations based on the SCC-DFTB/CHARMM level of theory yielded 15.3 kcal mol À1 energy storage.…”

Section: Photon Energy Storagementioning

confidence: 61%

“…Photon energy storage captured due to these torsional distortions along the polyene chain was estimated to be 15.6 kcal mol À1 . 83 Khrenova et al in DFT-and MP2-based QM/MM calculations demonstrated that calculated photonic energies converge to ca. 80 Blomgren and Larsson used the ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) CASSCF/AMBER type of calculations to obtain a stored energy of 22.4 kcal mol À1 .…”

Section: Photon Energy Storagementioning

confidence: 99%

“…81 In the calculations reported elsewhere 82 the chromophore-Glu113 complex stores between 12.7 and 20.0 kcal mol À1 . While Gascon and Batista have used a structural model based on the 1F88 crystal structure, in all other calculations 1HZX, 1U19 and/or 2G87 crystal structures have been utilized 34,45,46,80,82,83 due to their higher resolution. 34 Recently, Sekharan and Morokuma used the spectroscopy oriented configuration interaction (SORCI + Q) method along with B3LYP/MM optimized structures to find Batho to carry 19.5/26.1 kcal mol À1 with relaxed/frozen immediate vicinity of the chromophore, respectively.…”

Section: Photon Energy Storagementioning

confidence: 99%

See 1 more Smart Citation

Impacts of retinal polyene (de)methylation on the photoisomerization mechanism and photon energy storage of rhodopsin

Walczak

Andruniów

2015

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

Ab initio multiconfigurational quantum chemical methodology combined with molecular mechanics (CASPT2//CASSCF/AMBER) was applied to probe impacts of retinal protonated Schiff base (RPSB) polyene methylation and/or demethylation on the mechanism of photochemical isomerization in bovine rhodopsin. We have examined structural and spectroscopic properties of wild-type rhodopsin (with 11-cis-9,13-dimethyl-RPSB) and artificial rhodopsins, hosting four 11-cis-RPSB derivatives, 13-demethyl-, 9-demethyl-, 10-methyl-13-demethyl-, and 10-methyl-RPSB, evolving along the photoisomerization coordinate. It is found that the addition of 10-methyl or/and deletion of 9-/13-methyl groups do not appear to interfere structurally with the photoisomerization pathway in the S1 excited state. Remarkably, the two-mode space-saving mechanism initiated by bond order inversion and followed by asynchronous bicycle-pedal distortion in the RPSB backbone drives the photoreaction in all rhodopsin analogues studied here. However, methylation and/or demethylation is responsible for perturbation of excess energy deposited in the conical intersection structures. The analysis of photon energy stored by bathorhodopsin in synthetic pigments reveals that it is affected by steric crowding of methyl substituents in the RPSB backbone.

show abstract

“…How this receptor and these waters reorganize during activation needs to be solved. Perhaps a combination of computational [85, 86] and NMR studies [68, 87] will dominate in this area of investigation.…”

Section: Future Directionsmentioning

confidence: 99%

The G Protein-Coupled Receptor Rhodopsin: A Historical Perspective

Hofmann

Palczewski

2015

Methods in Molecular Biology

View full text Add to dashboard Cite

Rhodopsin is a key light-sensitive protein expressed exclusively in rod photoreceptor cells of the retina. Failure to express this transmembrane protein causes a lack of rod outer segment formation and progressive retinal degeneration, including the loss of cone photoreceptor cells. Molecular studies of rhodopsin have paved the way to understanding a large family of cell-surface membrane proteins called G protein-coupled receptors (GPCRs). Work started on rhodopsin over 100 years ago still continues today with substantial progress made every year. These activities underscore the importance of rhodopsin as a prototypical GPCR and receptor required for visual perception—the fundamental process of translating light energy into a biochemical cascade of events culminating in vision.

show abstract

QM/MM Study of the Structure, Energy Storage, and Origin of the Bathochromic Shift in Vertebrate and Invertebrate Bathorhodopsins

Cited by 38 publications

References 58 publications

Unusual kinetics of thermal decay of dim-light photoreceptors in vertebrate vision

Unusual kinetics of thermal decay of dim-light photoreceptors in vertebrate vision

Impacts of retinal polyene (de)methylation on the photoisomerization mechanism and photon energy storage of rhodopsin

The G Protein-Coupled Receptor Rhodopsin: A Historical Perspective

Contact Info

Product

Resources

About