@article {app9224905,
	title = {Atomistic Insight into the Role of Threonine 127 in the Functional Mechanism of Channelrhodopsin-2},
	journal = {Applied Sciences},
	volume = {9},
	year = {2019},
	abstract = {Channelrhodopsins (ChRs) belong to the unique class of light-gated ion channels. The structure of channelrhodopsin-2 from Chlamydomonas reinhardtii (CrChR2) has been resolved, but the mechanistic link between light-induced isomerization of the chromophore retinal and channel gating remains elusive. Replacements of residues C128 and D156 (DC gate) resulted in drastic effects in channel closure. T127 is localized close to the retinal Schiff base and links the DC gate to the Schiff base. The homologous residue in bacteriorhodopsin (T89) has been shown to be crucial for the visible absorption maximum and dark\&ndash;light adaptation, suggesting an interaction with the retinylidene chromophore, but the replacement had little effect on photocycle kinetics and proton pumping activity. Here, we show that the T127A and T127S variants of CrChR2 leave the visible absorption maximum unaffected. We inferred from hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and resonance Raman spectroscopy that the hydroxylic side chain of T127 is hydrogen-bonded to E123 and the latter is hydrogen-bonded to the retinal Schiff base. The C=N\&ndash;H vibration of the Schiff base in the T127A variant was 1674 cm\&minus;1, the highest among all rhodopsins reported to date. We also found heterogeneity in the Schiff base ground state vibrational properties due to different rotamer conformations of E123. The photoreaction of T127A is characterized by a long-lived P2380 state during which the Schiff base is deprotonated. The conservative replacement of T127S hardly affected the photocycle kinetics. Thus, we inferred that the hydroxyl group at position 127 is part of the proton transfer pathway from D156 to the Schiff base during rise of the P3530 intermediate. This finding provides molecular reasons for the evolutionary conservation of the chemically homologous residues threonine, serine, and cysteine at this position in all channelrhodopsins known so far.},
	issn = {2076-3417},
	doi = {10.3390/app9224905},
	url = {https://www.mdpi.com/2076-3417/9/22/4905},
	author = {Ehrenberg, David and Krause, Nils and Saita, Mattia and Bamann, Christian and Kar, Rajiv K. and Hoffmann, Kirsten and Heinrich, Dorothea and Schapiro, Igor and Heberle, Joachim and Schlesinger, Ramona}
}
@article {doi:10.1002/anie.201810266,
	title = {The Effective Conjugation Length Is Responsible for the Red/Green Spectral Tuning in the Cyanobacteriochrome Slr1393g3},
	journal = {Angewandte Chemie International Edition},
	volume = {58},
	year = {2019},
	pages = {1934-1938},
	abstract = {Abstract The origin of the spectral shift from a red- to a green-absorbing form in a cyanobacteriochrome, Slr1393g3, was identified by combined quantum mechanics/molecular mechanics simulations. This protein, related to classical phytochromes, carries the open-chain tetrapyrrole chromophore phycocyanobilin. Our calculations reveal that the effective conjugation length in the chromophore becomes shorter upon conversion from the red to the green form. This is related to the planarity of the entire chromophore. A large distortion was found for the terminal pyrrole rings A and D; however, the D ring contributes more strongly to the photoproduct tuning, despite a larger change in the twist of the A ring. Our findings implicate that the D ring twist can be exploited to regulate the absorption of the photoproduct. Hence, mutations that affect the D ring twist can lead to rational tuning of the photoproduct absorption, allowing the tailoring of cyanobacteriochromes for biotechnological applications such as optogenetics and bioimaging.},
	keywords = {chromophores, cyanobacteriochromes, hybrid QM/MM, spectral tuning, tetrapyrroles},
	doi = {10.1002/anie.201810266},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201810266},
	author = {Wiebeler, Christian and Aditya G. Rao and Wolfgang G{\"a}rtner and Schapiro, Igor}
}
@article {24116,
	title = {Nuclear spin-hyperpolarization generated in a flavoprotein under illumination: experimental field-dependence and theoretical level crossing analysis},
	journal = {Scientific Reports},
	volume = {9},
	year = {2019},
	pages = {18436},
	abstract = {The solid-state photo-chemically induced dynamic nuclear polarization (photo-CIDNP) effect generates non-equilibrium nuclear spin polarization in frozen electron-transfer proteins upon illumination and radical-pair formation. The effect can be observed in various natural photosynthetic reaction center proteins using magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy, and in a flavin-binding light-oxygen-voltage (LOV) domain of the blue-light receptor phototropin. In the latter system, a functionally instrumental cysteine has been mutated to interrupt the natural cysteine-involving photochemistry allowing for an electron transfer from a more distant tryptophan to the excited flavin mononucleotide chromophore. We explored the solid-state photo-CIDNP effect and its mechanisms in phototropin-LOV1-C57S from the green alga Chlamydomonas reinhardtii by using field-cycling solution NMR. We observed the\&nbsp;13C and, to our knowledge, for the first time,\&nbsp;15N photo-CIDNP signals from phototropin-LOV1-C57S. Additionally, the\&nbsp;1H photo-CIDNP signals of residual water in the deuterated buffer of the protein were detected. The relative strengths of the photo-CIDNP effect from the three types of nuclei,\&nbsp;1H,\&nbsp;13C and\&nbsp;15N were measured in dependence of the magnetic field, showing their maximum polarizations at different magnetic fields. Theoretical level crossing analysis demonstrates that anisotropic mechanisms play the dominant role at high magnetic fields.},
	author = {Ding, Yonghong and Kiryutin, Alexey S. and Yurkovskaya, Alexandra V. and Sosnovsky, Denis V. and Sagdeev, Renad Z. and Bannister, Saskia and Kottke, Tilman and Kar, Rajiv Kumar and Schapiro, Igor and Ivanov, Konstantin L. and Matysik, J{\"o}rg}
}
@article {24112,
	title = {OpenMolcas: From Source Code to Insight},
	journal = {Journal of Chemical Theory and ComputationJournal of Chemical Theory and Computation},
	volume = {15},
	year = {2019},
	note = {doi: 10.1021/acs.jctc.9b00532},
	month = {2019},
	pages = {5925 - 5964},
	publisher = {American Chemical Society},
	abstract = {In this Article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the Article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.In this Article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the Article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.},
	isbn = {1549-9618},
	url = {https://doi.org/10.1021/acs.jctc.9b00532},
	author = {Fdez. Galv{\'a}n, Ignacio and Vacher, Morgane and Alavi, Ali and Angeli, Celestino and Aquilante, Francesco and Jochen Autschbach and Bao, Jie J. and Bokarev, Sergey I. and Bogdanov, Nikolay A. and Carlson, Rebecca K. and Chibotaru, Liviu F. and Creutzberg, Joel and Dattani, Nike and Delcey, Micka{\"e}l G. and Dong, Sijia S. and Dreuw, Andreas and Freitag, Leon and Frutos, Luis Manuel and Gagliardi, Laura and Gendron, Fr{\'e}d{\'e}ric and Giussani, Angelo and Gonz{\'a}lez, Leticia and Grell, Gilbert and Guo, Meiyuan and Hoyer, Chad E. and Johansson, Marcus and Keller, Sebastian and Knecht, Stefan and Kova\v cevi{\'c}, Goran and K{\"a}llman, Erik and Li Manni, Giovanni and Lundberg, Marcus and Ma, Yingjin and Mai, Sebastian and Malhado, Jo{\~a}o Pedro and Malmqvist, Per {\r A}ke and Marquetand, Philipp and Mewes, Stefanie A. and Norell, Jesper and Olivucci, Massimo and Oppel, Markus and Phung, Quan Manh and Pierloot, Kristine and Plasser, Felix and Reiher, Markus and Sand, Andrew M. and Schapiro, Igor and Sharma, Prachi and Stein, Christopher J. and S{\o}rensen, Lasse Kragh and Truhlar, Donald G. and Ugandi, Mihkel and Ungur, Liviu and Valentini, Alessio and Vancoillie, Steven and Veryazov, Valera and Weser, Oskar and Weso{\l}owski, Tomasz A. and Widmark, Per-Olof and Wouters, Sebastian and Zech, Alexander and Zobel, J. Patrick and Lindh, Roland}
}
@article {molecules24091720,
	title = {QM/MM Benchmarking of Cyanobacteriochrome Slr1393g3 Absorption Spectra},
	journal = {Molecules},
	volume = {24},
	year = {2019},
	abstract = {Cyanobacteriochromes are compact and spectrally diverse photoreceptor proteins that are promising candidates for biotechnological applications. Computational studies can contribute to an understanding at a molecular level of their wide spectral tuning and diversity. In this contribution, we benchmark methods to model a 110 nm shift in the UV/Vis absorption spectrum from a red- to a green-absorbing form of the cyanobacteriochrome Slr1393g3. Based on an assessment of semiempirical methods to describe the chromophore geometries of both forms in vacuo, we find that DFTB2+D leads to structures that are the closest to the reference method. The benchmark of the excited state calculations is based on snapshots from quantum mechanics/molecular mechanics molecular dynamics simulations. In our case, the methods RI-ADC(2) and sTD-DFT based on CAM-B3LYP ground state calculations perform the best, whereas no functional can be recommended to simulate the absorption spectra of both forms with time-dependent density functional theory. Furthermore, the difference in absorption for the lowest energy absorption maxima of both forms can already be modelled with optimized structures, but sampling is required to improve the shape of the absorption bands of both forms, in particular for the second band. This benchmark study can guide further computational studies, as it assesses essential components of a protocol to model the spectral tuning of both cyanobacteriochromes and the related phytochromes.},
	issn = {1420-3049},
	doi = {10.3390/molecules24091720},
	url = {https://www.mdpi.com/1420-3049/24/9/1720},
	author = {Wiebeler, Christian and Schapiro, Igor}
}
@article {22577,
	title = {Spectroscopic Properties of Lumiflavin: A Quantum Chemical Study},
	journal = {Photochemistry and Photobiology},
	volume = {95},
	year = {2019},
	note = {doi: 10.1111/php.13023},
	month = {2018},
	pages = {662-674},
	publisher = {John Wiley \& Sons, Ltd},
	abstract = {Abstract In this work, the electronic structure and spectroscopic properties of lumiflavin are calculated using various quantum chemical methods. The excitation energies for ten singlet and triplet states as well as the analysis of the electron density difference are assessed using various wave function-based methods and density functionals. The relative order of singlet and triplet excited states is established on the basis of the coupled cluster method CC2. We find that at least seven singlet excited states are required to assign all peaks in the UV/Vis spectrum. In addition, we have studied the solvatochromic effect on the excitation energies and found differential effects except for the first bright excited state. Vibrational frequencies as well as IR, Raman and resonance Raman intensities are simulated and compared to their experimental counterparts. We have assigned peaks, assessed the effect of anharmonicity, and confirmed the previous assignments in case of the most intense transitions. Finally, we have studied the NMR shieldings and established the effect of the solvent polarity. The present study provides data for lumiflavin in the gas phase and in implicit solvent model that can be used as a reference for the protein-embedded flavin simulations and assignment of experimental spectra.},
	isbn = {0031-8655},
	url = {https://doi.org/10.1111/php.13023},
	author = {Kar, Rajiv Kumar and Borin, Veniamin A. and Ding, Yonghong and Matysik, J{\"o}rg and Schapiro, Igor}
}
@article {C9PP00223E,
	title = {Synthesis, spectroscopy and QM/MM simulations of a biomimetic ultrafast light-driven molecular motor},
	journal = {Photochem. Photobiol. Sci.},
	volume = {18},
	year = {2019},
	pages = {2259-2269},
	publisher = {The Royal Society of Chemistry},
	abstract = {A molecular motor potentially performing a continuous unidirectional rotation is studied by a multidisciplinary approach including organic synthesis, transient spectroscopy and excited state trajectory calculations. A stereogenic center was introduced in the N-alkylated indanylidene{\textendash}pyrroline Schiff base framework of a previously investigated light-driven molecular switch in order to achieve the unidirectional CC rotary motion typical of Feringa{\textquoteright}s motor. Here we report that the specific substitution pattern of the designed chiral molecule must critically determine the unidirectional efficiency of the light-induced rotary motion. More specifically, we find that a stereogenic center containing a methyl group and a hydrogen atom as substituents does not create a differential steric effect large enough to fully direct the motion in either the clockwise or counterclockwise direction especially along the E {\textrightarrow} Z coordinate. However, due to the documented ultrafast character and electronic circular dichroism activity of the investigated system, we find that it provides the basis for development of a novel generation of rotary motors with a biomimetic framework and operating on a picosecond time scale.},
	doi = {10.1039/C9PP00223E},
	url = {http://dx.doi.org/10.1039/C9PP00223E},
	author = {Schapiro, Igor and Gueye, Moussa and Paolino, Marco and Fusi, Stefania and Marchand, Gabriel and Haacke, Stefan and Martin, M. Elena and Mark Huntress and Vysotskiy, Victor P. and Veryazov, Valera and L{\'e}onard, J{\'e}r{\'e}mie and Olivucci, Massimo}
}
