Protonation depending photochemistry in rhodopsin and phytochrome photoreceptors

Principal Investigator: Prof. Dr. Igor Schapiro (HUJI)

The goal of this project is derive a molecular-level understanding of how excitation effects protonation dynamics in retinal proteins and phytochromes. Both of these photoreceptor proteins engage double-bond photoisomerization as a common activation mechanism that leads to altered molecular interactions and proton transfer. To this end we will use hybrid quantum mechanics/molecular mechanics methods to simulate static spectra as well as dynamics. We will focus on the retinal proteins Channelrhodopsin, the sodium pump KR2 and the chloride pump NmHR as well as the phytochromes Agp1, Agp2 and Cph1.

Publications

2021 - 2024

Adam, S., Wiebeler, C., and Schapiro, I. (2021). Structural factors determining the absorption spectrum of channelrhodopsins: A Case study of the chimera C1C2. J Chem Theory Comput, 17, 10, 6302-6313. doi: 10.1021/acs.jctc.1c00160.

Asido, M., Kar, R. K., Kriebel, C. N., Braun, M., Glaubitz, C., Schapiro, I., and Wachtveitl, J. (2021). Transient Near-UV Absorption of the Light-Driven Sodium Pump Krokinobacter eikastus Rhodopsin 2: A Spectroscopic Marker for Retinal Configuration. J Phys Chem Lett, 12, 27, 6284-6291. doi: 10.1021/acs.jpclett.1c01436. [as Mercator Fellow]

Buhrke, D., Lahav, Y., Rao, A., Ruf, J., Schapiro, I. and Hamm, P. (2023). Transient 2D IR Spectroscopy and Multiscale Simulations Reveal Vibrational Couplings in the Cyanobacteriochrome Slr1393-g3. J Am Chem Soc, 145, 29: 15766-15775. doi: 10.1021/jacs.3c00896.

Church, J.R., Olsen, J.M.H. and Schapiro, I. (2021). The Impact of Retinal Configuration on the Protein-Chromophore Interactions in Bistable Jumping Spider Rhodopsin-1. Molecules, 27, 1: doi: 10.3390/molecules27010071.

Church, J.R., Olsen, J.M.H. and Schapiro, I. (2023). Induction effects on the absorption maxima of photoreceptor proteins. Biophys Physicobiol, 20: e201007. doi: 10.2142/biophysico.bppb-v20.s007.

Deree, Y., Bogoslavsky, B., Schapiro, I. and Gidron, O. (2024). The photochemistry and photophysics of benzoyl-carbazole. Phys Chem Chem Phys, 26, 26: 18048-18053. doi: 10.1039/d4cp01781a.

Filiba, O., Borin, V.A. and Schapiro, I. (2022). The involvement of triplet states in the isomerization of retinaloids. Phys Chem Chem Phys. doi: 10.1039/D2CP03791B.

Gemeinhardt, F.G., Lahav, Y., Schapiro, I., Noy, D., Müh, F., Lindorfer, D. and Renger, T. (2023). Short-Range Effects in the Special Pair of Photosystem II Reaction Centers: The Nonconservative Nature of Circular Dichroism. J Phys Chem Lett, 14, 51: 11758-11767. doi: 10.1021/acs.jpclett.3c02693.

Juarez, J.F.B., Judge, P.J., Adam, S., Axford, D., Vinals, J., Birch, J., Kwan, T.O.C., Hoi, K.K., Yen, H.-Y., Vial, A., Milhiet, P.-E., Robinson, C.V., Schapiro, I., Moraes, I., and Watts, A. (2021). Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization. Nat Commun 12, 629. doi: 10.1038/s41467-020-20596-0. [as Mercator Fellow]

Mackintosh, M.J., Hoischen, D., Martin, H.D., Schapiro, I. and Gärtner, W. (2024). Merocyanines form bacteriorhodopsins with strongly bathochromic absorption maxima. Photochem Photobiol Sci, 23, 1: 31-53. doi: 10.1007/s43630-023-00496-0.

Mous, S., Gotthard, G., Ehrenberg, D., Sen, S., Weinert, T., Johnson, P.J.M., James, D., Nass, K., Furrer, A., Kekilli, D., Ma, P., Brünle, S., Casadei, C.M., Martiel, I., Dworkowski, F., Gashi, D., Skopintsev, P., Wranik, M., Knopp, G., Panepucci, E., Panneels, V., Cirelli, C., Ozerov, D., Schertler, G., Wang, M., Milne, C., Standfuss, J., Schapiro, I., Heberle, J., and Nogly, P. (2022). Dynamics and mechanism of a light-driven chloride pump. Science. doi: 10.1126/science.abj6663.

Mroginski, M.A., Adam, S., Amoyal, G.S., Barnoy, A., Bondar, A.-N., Borin, V.A., Church, J.R., Domratcheva, T., Ensing, B., Fanelli, F., Ferré, N., Filiba, O., Pedraza-González, L., González, R., González-Espinoza, C.E., Kar, R.K., Kemmler, L., Kim, S.S., Kongsted, J., Krylov, A.I., Lahav, Y., Lazaratos, M., NasserEddin, Q., Navizet, I., Nemukhin, A., Olivucci, M., Olsen, J.M.H., Pérez de Alba Ortíz, A., Pieri, E., Rao, A.G., Rhee, Y.M., Ricardi, N., Sen, S., Solov'yov, I.A., De Vico, L., Wesolowski, T.A., Wiebeler, C., Yang, X., and Schapiro, I. (2021). Frontiers in Multiscale Modeling of Photoreceptor Proteins. Photochem Photobiol, 97: 243-269. doi: 10.1111/php.13372.

Mulder, M., Hwang, S., Broser, M., Brunle, S., Skopintsev, P., Schattenberg, C., Schnick, C., Hartmann, S., Church, J., Schapiro, I., Dworkowski, F., Weinert, T., Hegemann, P., Sun, H. and Standfuss, J. (2025). Structural Insights Into the Opening Mechanism of C1C2 Channelrhodopsin. J Am Chem Soc, 147, 1: 1282-1290. doi: 10.1021/jacs.4c15402.

Palombo, R., Barneschi, L., Pedraza-González, L., Padula, D., Schapiro, I. and Olivucci, M. (2022). Retinal chromophore charge delocalization and confinement explain the extreme photophysics of Neorhodopsin. Nat Commun, 13, 1: 6652. doi: 10.1038/s41467-022-33953-y.

Rao, A.G. and Schapiro, I. (2022). Photoisomerization of phytochrome chromophore models: an XMS-CASPT2 study. Phys Chem Chem Phys. doi: 10.1039/D2CP04249E.

Ricardi, N., González-Espinoza, C., Adam, S., Church, J.R., Schapiro, I. and Wesolowski, T.A. (2023). Embedding Nonrigid Solutes in an Averaged Environment: A Case Study on Rhodopsins. J Chem Theory Comput, 19, 15: 5289-5302. doi: 10.1021/acs.jctc.3c00285.

Riebe, S., Adam, S., Roy, B., Maisuls, I., Daniliuc, C. G., Dubbert, J., Strassert, C.A., Schapiro, I., and Voskuhl, J. (2021). Bridged Aromatic Oxo‐and Thioethers with Intense Emission in Solution and the Solid State. Chem Asian J, 16, 2307-2313. doi: 10.1002/asia.202100492.

Sela, M., Church, J.R., Schapiro, I. and Schneidman-Duhovny, D. (2024). RhoMax: Computational Prediction of Rhodopsin Absorption Maxima Using Geometric Deep Learning. J Chem Inf Model, 64, 12: 4630-4639. doi: 10.1021/acs.jcim.4c00467.

Sokolovski, S.G., Zherebtsov, E.A., Kar, R.K., Golonka, D., Stabel, R., Chichkov, N.B., Gorodetsky, A., Schapiro, I., Möglich, A, and Rafailov, E. U. (2021). Two-photon conversion of a bacterial phytochrome. Biophys J, 120, 5: 964-974. doi: 10.1016/j.bpj.2021.01.028.

Yang, Y., Stensitzki, T., Sauthof, L., Schmidt, A., Piwowarski, P., Velazquez Escobar, F., Michael, N., Nguyen, A.D., Szczepek, M., Brünig, F. N., Netz, R.R., Mroginski, M.A., Adam, S., Bartl, F.J., Schapiro, I., Hildebrandt, P., Scheerer, P., and Heyne, K. (2022). Ultrafast proton-coupled isomerization in the phototransformation of phytochrome. Nat Chem. doi: 10.1038/s41557-022-00944-x.

2017 - 2020 (as Mercator Fellow)

Battocchio G., González R., Rao A.G., Schapiro I., Mroginski M.A. (2020). Dynamic Properties of the Photosensory Domain of Deinococcus radiodurans Bacteriophytochrome. J. Phys. Chem. B 124, 1740–1750; doi: 10.1021/acs.jpcb.0c00612

Borin V., Wiebeler C., Schapiro I. (2018). A QM/MM study of the initial excited state dynamics of greenabsorbing proteorhodopsin. Faraday Discuss. 207, 137–152; doi: 10.1039/C7FD00198C

Ehrenberg, D., Krause, N., Saita, M., Bamann, C., Kar, R.K., Hoffmann, K., Heinrich, D., Schapiro, I., Heberle, J., and Schlesinger, R. (2019) Atomistic insight into the role of threonine 127 in the functional mechanism of channelrhodopsin-2. Appl. Sci., 9 (22), 4905; https://doi.org/10.3390/app9224905.

Guo, Y., Wolff, F. E., Schapiro, I., Elstner, M., Marazzi, M. (2018). Different hydrogen bonding environments of the retinal protonated Schiff base control the photoisomerization in channelrhodopsin-2. Phys Chem Chem Phys 20, 27501-27509, doi: 10.1039/c8cp05210g.

Kaufmann, J.C.D., Krause B.S., Adam S., Ritter E., Schapiro I., Hegemann P. and Bartl F.J. (2020). Modulation of Light Energy Transfer from Chromophore to Protein in the Channelrhodopsin ReaChR. Biophysical Journal; doi: 10.1016/j.bpj.2020.06.031

Kraskov A., Nguyen A. D., Goerling J., Buhrke D., Velazquez F., Fernandez M., Michael N., Sauthof L. Schmidt A., Piwowarski P., Yang Y., Stensitzki T., Adam S., Bartl F., Schapiro I., Heyne K., Siebert F., Scheerer P., Mroginski M.A, and Hildebrandt P. (2020). Intramolecular Proton Transfer Controls Protein Structural Changes in Phytochrome. Biochemistry 59, 1023–1037; doi: 10.1021/acs.biochem.0c00053

Nogly, P., Weinert, T., James, D., Carbajo, S., Ozerov, D., Furrer, A., Gashi, D., Borin, V., Skopintsev, P., Jaeger, K., Nass, K., Bath, P., Bosman, R., Koglin, J., Seaberg, M., Lane, T., Kekilli, D., Brunle, S., Tanaka, T., Wu, W., Milne, C., White, T., Barty, A., Weierstall, U., Panneels, V., Nango, E., Iwata, S., Hunter, M., Schapiro, I., Schertler, G., Neutze, R., and Standfuss, J. (2018). Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser. Science 361, 6398; doi: 10.1126/science.aat0094.

Schnedermann, C., Yang, X., Liebel, M., Spillane, K. M., Lugtenburg, J., Fernandez, I., Valentini, A., Schapiro, I., Olivucci, M., Kukura, P., Mathies, R. A. (2018). Evidence for a vibrational phase isotope effect on the photochemistry of vision. Nature Chemistry, 2018, 10, 449-455, doi: 10.1038/s41557-018-0014-y.

Skopintsev, P., Ehrenberg, D., Weinert, T., James, D., Kar, R. K., Johnson, P. J. M., Ozerov, D., Furrer, A., Martiel, I., Dworkowski, F., Nass, K., Knopp, G., Cirelli, C., Arrell, C., Gashi, D., Mous, S., Wranik, M., Gruhl, T., Kekilli, D., Brünle, S., Deupi, X., Schertler, G. F. X., Benoit, R. M., Panneels, V., Nogly, P., Schapiro, I., Milne, C., Heberle, J., and Standfuss, J. (2020). Femtosecond-to-millisecond structural changes in a light-driven sodium pump. Nature. doi: 10.1038/s41586-020-2307-8.

Stensitzki, T., Adam, S., Schlesinger, R., Schapiro, I., and Heyne, K. (2020) Ultrafast Backbone Protonation in Channelrhodopsin-1 Captured by Polarization Resolved Fs Vis-pump-IR-Probe Spectroscopy and Computational Methods. Molecules 25, 848; doi: 10.3390/molecules25040848.

Wiebeler, Ch., Rao, A. G., Gärtner, W., and Schapiro, I. (2018). The Effective Conjugation Length is Responsible for the Red/Green Spectral Tuning in the Cyanobacteriochrome Slr1393g3. Angewandte Chemie 58(7), 1934-1938, doi: org/10.1002/anie.201810266.

Wiebeler C., Schapiro I. (2019). QM/MM Benchmarking of Cyanobacteriochrome Slr1393g3 Absorption Spectra. Molecules 24, 1720; doi: 10.3390/molecules24091720.

Xu, X., Port, A., Wiebeler, Ch., Kai-Hong Zhao, K.-H., Schapiro, I., and Gärtner, W. (2020). Structural elements regulating the photochromicity in a cyanobacteriochrome. PNAS117 (5)2432-2440, doi: 10.1073/pnas.1910208117.