When Light Falls in LOV:  A Quantum Mechanical/Molecular Mechanical Study of Photoexcitation in Phot-LOV1 of <i>Chlamydomonas reinhardtii</i>

Dittrich, Markus; Freddolino, Peter L.; Schulten, Klaus

doi:10.1021/jp050943o

Cited by 66 publications

(94 citation statements)

References 45 publications

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“…They deduced from their calculation results that the reaction pathway proceeds via the triplet T1-state of the FMN, and that the process of adduct formation involves intermediate radicals rather than ionic species. Dittrich et al [30] studied the early steps of the photocycle by performing combined quantum mechanical/molecular mechanical (QM/MM) simulations of a complete LOV1-domain from C. reinhardtii. They investigated the electronic properties and initial structural changes that follow blue-light absorption, and concluded from their calculation results that the pathway for cysteinyl-FMN(CFN) adduct formation proceeds via a neutral radical state, generated by H-atom transfer from the reactive Cys57-residue to the FMN-chromophore.…”

Section: Introductionmentioning

confidence: 99%

Signals of LOV1: a computer simulation study on the wildtype LOV1-domain of Chlamydomonas reinhardtii and its mutants

2011

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Phototropins are photoreceptors regulating the blue-light response in plants and bacteria. They consist of two LOV (light oxygen voltage sensitive) domains each containing a non-covalently bound flavin-mononucleotide (FMN) chromophore, which are connected to a serine/threonine-kinase. Upon illumination, the LOV-domains undergo conformational changes, triggering a signal cascade in the organism through kinase activation. Here, we present results from molecular dynamics simulations in which we investigate the signal transduction pathway of the wildtype LOV1-domain of Chlamydomonas reinhardtii and a methyl-mercaptan (MM) adduct of its Cys57Gly-mutant at the molecular level. In particular, we analyzed the effect of covalent-bond formation between the reactive cysteine Cys57 and the FMN-reaction center, as well as the subsequent charge redistribution, on the spatio-dynamical behavior of the LOV1-domain. We compare the calculation results with experimental data and demonstrate that these adduct state characteristics have an important influence on the response of this photosensor. The light-induced changes implicate primarily an alteration of the surface charge distribution through rearrangement of the highly flexible Cα-, Dα- and Eα-helices including the Glu51-Lys91-salt bridge on the hydrophilic side of the protein domain and a β-sheet tightening process via coupling of the Aβ- and Bβ-strands. Our findings confirm the aptitude of the LOV1-domain to function as a dimerization partner, allowing the green alga to adapt its reproduction and growth speed to the environmental conditions.

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Section: Introductionmentioning

confidence: 99%

Signals of LOV1: a computer simulation study on the wildtype LOV1-domain of Chlamydomonas reinhardtii and its mutants

2011

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“…This issue has subsequently been investigated in more detail in a series of theoretical studies. Dittrich et al [20] performed quantum chemical calculations for the first excited triplet state of the FMN-related model compound lumiflavin at the ROHF/6-31G(2d,2p) level of theory and concluded from analyzing the resulting Mulliken spin populations that a significant fraction of unpaired spin density is localized on the C4a as well as the C8 position of lumiflavin. Salzmann et al [76,77] demonstrated that not only the ordering of low-lying potential energy hypersurfaces but also the mechanism of triplet generation in the case of FMN-related compounds significantly depends on the environment.…”

Section: Resultsmentioning

confidence: 99%

“…They deduced from their calculation results that the reaction pathway takes place via the triplet T1-state of the FMN and that the process of adduct formation involves rather intermediate radicals instead of ionic species. Dittrich et al [20] studied the early steps of the photocycle by performing combined quantum mechanical/molecular mechanical (QM/ MM) simulations of a complete LOV1 domain from C. reinhardtii. They investigated the electronic properties and initial structural changes that follow blue-light absorption and concluded from their calculation results that the pathway for cysteinyl-FMN adduct formation proceeds via a neutral radical state generated by H atom transfer from the reactive Cys57 residue to the FMN chromophore.…”

Section: Introductionmentioning

confidence: 99%

Effect of computational methodology on the conformational dynamics of the protein photosensor LOV1 from Chlamydomonas reinhardtii

2011

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LOV domains are the light-sensitive protein domains of plant phototropins and bacteria. They photochemically form a covalent bond between a flavin mononucleotide (FMN) chromophore and a cysteine, attached to the apo-protein, upon irradiation with blue light, which triggers a signal in the adjacent kinase. Although their signaling state has been well characterized through experimental means, their signal transduction pathway as well as dark-state activity are generally only poorly understood. Here we show results from molecular dynamics simulations where we investigated the effect of thermostating and long-range electrostatics on the solution structure and dynamical behavior of the wild-type LOV1 domain from the green algae Chlamydomonas reinhardtii in the dark. We demonstrate that these computational issues can dramatically affect the conformational fluctuations of such protein domains by suppressing configurations far from equilibrium or destabilizing local configurations, leading to artificial changes of the protein secondary structure as well as the H-bond network formed by the amino acids and the FMN. By comparing our calculation results with recent experimental data, we show that the noninvasive thermostating strategy, where the protein solute is only indirectly coupled to the thermostat via the solvent, in conjunction with the particle-mesh Ewald technique, provides dark-state conformers, which are in consistency with experimental observations. Moreover, our calculations indicate that the LOV1 domains can alter the intersystem crossing rate and rate of adduct formation by adjusting the population distribution of these dark-state conformers. This might permit them to function as a modulator of the signal intensity under low light conditions.

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“…These receptors mediate plant phototropism and contain two light, oxygen, and voltage (LOV)-sensitive domains as photoactive elements. The Phot-LOV1 domain from Chlamidomonas reinhardtii was studied [160]. The electronic properties and structural changes that follow blue-light absorption were studied by combined QM/MM simulations of the photocycle of the Phjt-LOV1 domain of C. reinhardtii [160].…”

Section: The Pigments Cofactors and So Onmentioning

confidence: 99%

“…The Phot-LOV1 domain from Chlamidomonas reinhardtii was studied [160]. The electronic properties and structural changes that follow blue-light absorption were studied by combined QM/MM simulations of the photocycle of the Phjt-LOV1 domain of C. reinhardtii [160]. This allowed one to resolve the structural changes and study the electronic processes accompanying flavin-cysteinyl adduct formation.…”

Section: The Pigments Cofactors and So Onmentioning

confidence: 99%

Role of quantum chemical calculations in molecular biophysics with a historical perspective

Kukushkin

Jalkanen

2009

Theor Chem Acc

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We discuss how the basic principles of quantum chemistry and quantum mechanics can be and have been applied to a variety of problems in molecular biophysics. First, the historical development of quantum concepts in biophysics is discussed. Next, we describe a series of interesting applications of quantum chemical methods for studying biologically active molecules, molecular structures and some of the important processes which play a role in living organisms. We discuss the application of quantum chemistry to such processes as energy storage and transformation, and the transmission of genetic information. Quantum chemical approaches are essential to comprehend and understand the molecular nature of these processes. To conclude our work, we present a short discussion of the perspectives of quantum chemical methods in modern biophysics, the field of experimental and theoretical chiral vibrational and electronic spectroscopy.

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When Light Falls in LOV: A Quantum Mechanical/Molecular Mechanical Study of Photoexcitation in Phot-LOV1 of Chlamydomonas reinhardtii

Cited by 66 publications

References 45 publications

Signals of LOV1: a computer simulation study on the wildtype LOV1-domain of Chlamydomonas reinhardtii and its mutants

Signals of LOV1: a computer simulation study on the wildtype LOV1-domain of Chlamydomonas reinhardtii and its mutants

Effect of computational methodology on the conformational dynamics of the protein photosensor LOV1 from Chlamydomonas reinhardtii

Role of quantum chemical calculations in molecular biophysics with a historical perspective

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