Laboratory of Biomolecular Recognition

Detailed laboratory website: https://biorecognition.structbio.org/index.html

Our goal is to understand how biological functions relate to structures of biomolecules and their interactions. We therefore concentrate on determination of biomolecular structures and dynamics of their behavior and study specific protein-protein and protein-DNA interactions, their mutual recognition. In our work, we take advantage of experimental and computational methods of protein engineering, structural biology, bionformatics, and molecular modeling.

In the lab, we run several projects:

• Cytokines. We study structure-function relationships of cytokines from the family of Interleukin 10. These signaling proteins and their receptors are important in the immunity response to viral and bacterial infection, and errors in their regulation cause serious autoimmune and/or allergic health disorders and may even promote malignancy. We concentrate on structural aspects of the cytokine interactions, determine their crystal structures, and modify their molecules to make them more stable. We also apply methods of directed evolution (ribosome and yeast display) to develop de novo proteins binding specifically FIL-10 cytokines or their receptors.
• Bioinformatics. The lab concentrates on structural analysis of nucleic acids, DNA and RNA, and on hydration around proteins and nucleic acids.

Nucleic acids are structurally plastic molecules. To identify their structural polymorphisms we analyzed structures of dinucleotide building blocks in thousands of crystal structures. We clustered them into so called conformational classes NtC and so called structural alphabet CANA. The work is summarized in several publications and the results are available on the website dnatco.org.

Hydration. Water molecules in the first hydration shell of amino acids residues in proteins and dinucleotides in DNA are well ordered and the structure of the shell depends on the biomolecular structure and its sequence.

• Single stranded DNA (ssDNA). ssDNA is known to play important yet largely unknown functions in genome regulation. We study one specific class of bacterial ssDNA, so called Repetitive extragenic palindromes (REP) and their associated enzyme, tyrosine transposase (RAYT).
• Dynamics of Biomolecules. In collaboration with colleagues at ELI-Beamlines, we explore new frontiers in light and optics to create breakthrough science about biomolecular dynamics from femtoseconds to seconds.

Collaborations. The lab is a part of the Institute of Biotechnology of the Czech Academy of Sciences located at the BIOCEV center. It participates in the research program "Structural Biology and Protein Engineering”. We are also active in Instruct-ERIC and ELIXIR (3D-Bioinfo community) infrastructural projects.

2024

• Andrikopoulos PC, Čabart P. The chromatin remodeler SMARCA5 binds to d-block metal supports: Characterization of affinities by IMAC chromatography and QM analysis. PLoS One. 2024 Oct 7;19(10):e0309134. doi: 10.1371/journal.pone.0309134. PMID: 39374200; PMCID: PMC11458017.

• Krattenmacher J, Lera-Ramirez M, Beber A, Herynek S, Grycova L, Liu X, Neuzil P, Nedelec F, Diez S, Braun M, Lansky Z. Ase1 selectively increases the lifetime of antiparallel microtubule overlaps. Curr Biol. 2024 Sep 9;34(17):4071-4080.e6. doi: 10.1016/j.cub.2024.07.055. Epub 2024 Aug 12. PMID: 39137787.

2023

• Huliciak, M., Biedermanova, L., Berdar, D., Herynek, S., Kolarova, L., Tomala, J., Mikulecky, P., & Schneider, B. (2023)."Combined in vitro and cell-based selection display method producing specific binders against IL-9 receptor in high yields."FEBS J. https://doi.org/10.1111/febs.16726

• Chaudhari, A. S., Chatterjee, A., Domingos, C. A. O., Andrikopoulos, P. C., Liu, Y., Andersson, I., Schneider, B., Lorenz-Fonfria, V. A., & Fuertes, G. (2023)."Genetically encoded non-canonical amino acids reveal asynchronous dark reversion of chromophore, backbone and side-chains in EL222." Protein Sci, e4590. https://doi.org/10.1002/pro.4590

• Kolenko P, Mikulecký P, Pham PN, Malý M, Schneider B. Diffraction anisotropy and paired refinement: crystal structure of H33, a protein binder to interleukin 10. J Appl Crystallogr. 2023 Jun 16;56(Pt 4):1261-1266. doi: 10.1107/S160057672300479X. PMID: 37555209; PMCID: PMC10405593.

• Liu, Y., Chaudhari, A. S., Chatterjee, A., Andrikopoulos, P. C., Picchiotti, A., Rebarz, M., Kloz, M., Lorenz-Fonfria, V. A., Schneider, B., & Fuertes, G. (2023)."Sub-Millisecond Photoinduced Dynamics of Free and EL222-Bound FMN by Stimulated Raman and Visible Absorption Spectroscopies."Biomolecules, 13(1). https://doi.org/10.3390/biom13010161

• Pham PN, Zahradník J, Kolářová L, Schneider B, Fuertes G. Regulation of IL-24/IL-20R2 complex formation using photocaged tyrosines and UV light. Front Mol Biosci. 2023 Jul 7;10:1214235. doi: 10.3389/fmolb.2023.1214235. PMID: 37484532; PMCID: PMC10361524.

• Schneider, B., Sweeney, BA., Bateman, A., Cerny, J., Zok, T., Szachniuk, M.(2023)"When will RNA get its AlphaFold moment?"Nucleic Acids Res. doi: 10.1093/nar/gkad726.

• Svoboda J, Berdár D, Kolenko P, Černý J, Nováková Z, Pavlíček J, Schneider B. Conformation-based refinement of 18-mer DNA structures. Acta Crystallogr D Struct Biol. 2023 Jul 1;79(Pt 7):655-665. doi: 10.1107/S2059798323004679. Epub 2023 Jun 20. PMID: 37338420; PMCID: PMC10306069.

2022

• Berman, H. M., Lawson, C. L., Schneider, B. (2022). "Developing Community Resources for Nucleic Acid Structures." Life (Basel), 12(4). https://doi.org/10.3390/life12040540

• Biedermannova, L., Cerny, J., Maly, M., Nekardova, M., & Schneider, B. (2022). "Knowledge-based prediction of DNA hydration using hydrated dinucleotides as building blocks." Acta Crystallogr D Struct Biol, 78(Pt 8), 1032-1045. https://doi.org/10.1107/S2059798322006234

• Kipouros, I., Stanczak, A., Ginsbach, J. W., Andrikopoulos, P. C., Rulisek, L., & Solomon, E. I. (2022). "Elucidation of the tyrosinase/O2/monophenol ternary intermediate that dictates the monooxygenation mechanism in melanin biosynthesis." Proc Natl Acad Sci U S A, 119(33), e2205619119. https://doi.org/10.1073/pnas.2205619119

• Kolarova, L., Zahradnik, J., Huliciak, M., Mikulecky, P., Peleg, Y., Shemesh, M., Schreiber, G., & Schneider, B. (2022)."De novo developed protein binders mimicking Interferon lambda signaling." FEBS J, 289(9), 2672-2684. https://doi.org/10.1111/febs.16300

• VanDyke, D., Iglesias, M., Tomala, J., Young, A., Smith, J., Perry, J. A., Gebara, E., Cross, A. R., Cheung, L. S., Dykema, A. G., Orcutt-Jahns, B. T., Henclova, T., Golias, J., Balolong, J., Tomasovic, L. M., Funda, D., Meyer, A. S., Pardoll, D. M., Hester, J., Issa, F., Hunter, C. A., Anderson, M. S., Bluestone, J. A., Raimondi, G., & Spangler, J. B. (2022)."Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection." Cell Rep, 41(3), 111478. https://doi.org/10.1016/j.celrep.2022.111478

2021

• Andrikopoulos, P. C., Chaudhari, A. S., Liu, Y., Konold, P. E., Kennis, J. T. M., Schneider, B., & Fuertes, G. (2021). QM calculations predict the energetics and infrared spectra of transient glutamine isomers in LOV photoreceptors. Phys Chem Chem Phys, 23(25), 13934-13950. https://doi.org/10.1039/d1cp00447f

• Dedecek, J., Tabor, E., Andrikopoulos, P. C., Sklenak, S. (2021). "Splitting dioxygen over distant binuclear transition metal cationic sites in zeolites. Effect of the transition metal cation." Int. Journal of Quantum Chemistry, 121(10). https://doi.org/ARTN e2661110.1002/qua.26611 (ASEP)

• Kolarova, L., Zahradnik, J., Huliciak, M., Mikulecky, P., Peleg, Y., Shemesh, M., Schreiber, G., Schneider, B. (2021). "De novo developed protein binders mimicking Interferon lambda signaling." FEBS J. https://doi.org/10.1111/febs.16300 (ASEP)

• Phuong, N.P., Huličiak, M., Biedermannová, L.,  Černý, J., Charnavets T., Fuertes, G., Herynek, Š., Kolářová, L., Kolenko P.,  Pavlíček J., Zahradník, J., Mikulecky, P., Schneider, B. (2021)"Protein Binder (ProBi) as a New Class of Structurally Robust Non-Antibody Protein Scaffold for Directed Evolution Viruses 13(2), 190

• Zahradnik, J., Dey, D., Marciano, S., Kolarova, L., Charendoff, C. I., Subtil, A., & Schreiber, G. (2021). "A Protein-Engineered, Enhanced Yeast Display Platform for Rapid Evolution of Challenging Targets." ACS Synth Biol. https://doi.org/10.1021/acssynbio.1c00395

2020

• Andrikopoulos, P. C., Y. Liu, A. Picchiotti, N. Lenngren, M. Kloz, A. S. Chaudhari, M. Precek, M. Rebarz, J. Andreasson, J. Hajdu, B. Schneider and G. Fuertes (2020). "Femtosecond-to-nanosecond dynamics of flavin mononucleotide monitored by stimulated Raman spectroscopy and simulations." Phys Chem Chem Phys 22(12), 6538-6552.

• Cerny, J., Bozikova, P., Maly, M., Tykac, M., Biedermannova, L., & Schneider, B. (2020). "Structural alphabets for conformational analysis of nucleic acids available at dnatco.datmos.org." Acta Crystallogr D Struct Biol, 76(Pt 9), 805-813.

• Cerny, J., P. Bozikova, J. Svoboda and B. Schneider (2020). "A unified dinucleotide alphabet describing both RNA and DNA structures." Nucleic Acids Research.

• Orengo, C., Velankar, S., Wodak, S., Zoete, V., Bonvin, A., Elofsson, A., Feenstra, K. A., Gerloff, D. L., Hamelryck, T., Hancock, J. M., Helmer-Citterich, M., Hospital, A., Orozco, M., Perrakis, A., Rarey, M., Soares, C., Sussman, J. L., Thornton, J. M., Tuffery, P., Tusnady, G., Wierenga, R., Salminen, T., & Schneider, B. (2020). "A community proposal to integrate structural bioinformatics activities in ELIXIR (3D-Bioinfo Community)." F1000Res, 9.

• Pizl, M., Picchiotti, A., Rebarz, M., Lenngren, N., Yingliang, L., Zalis, S., Kloz, M., & Vlcek, A. (2020). "Time-Resolved Femtosecond Stimulated Raman Spectra and DFT Anharmonic Vibrational Analysis of an Electronically Excited Rhenium Photosensitizer." J Phys Chem A, 124(7), 1253-1265.

2019

• Fuertes, G., L. Nevola and S. Esteban-Martín (2019). Perspectives on drug discovery strategies based on IDPs. Intrinsically Disordered Proteins: 275-327.

• Zahradnik, J., L. Kolarova, Y. Peleg, P. Kolenko, S. Svidenska, T. Charnavets, T. Unger, J. L. Sussman and B. Schneider (2019). "Flexible regions govern promiscuous binding of IL-24 to receptors IL-20R1 and IL-22R1." FEBS J 286(19): 3858-3873.

2018

• Fuertes, G., N. Banterle, K. M. Ruff, A. Chowdhury, R. V. Pappu, D. I. Svergun and E. A. Lemke (2018). "Comment on "Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water"." Science 361(6405).

• Palyzova, A., J. Zahradnik, H. Maresova, L. Sokolova, E. Kyslikova, M. Grulich, V. Stepanek, T. Rezanka and P. Kyslik (2018). "Potential of the strain Raoultella sp. KDF8 for removal of analgesics." Folia Microbiol (Praha) 63(3): 273-282.

• Schneider, B., P. Boaeikova, I. Necasova, P. Cech, D. Svozil and J. Cerny (2018). "A DNA structural alphabet provides new insight into DNA flexibility." Acta Crystallogr D Struct Biol 74(Pt 1): 52-64.

• Zahradnik, J., L. Kolarova, H. Parizkova, P. Kolenko and B. Schneider (2018). "Interferons type II and their receptors R1 and R2 in fish species: Evolution, structure, and function." Fish Shellfish Immunol 79: 140-152.

• Zahradnik, J., P. Kolenko, A. Palyzova, J. Cerny, L. Kolarova, E. Kyslikova, H. Maresova, M. Grulich, J. Nunvar, M. Sulc, P. Kyslik and B. Schneider (2018). "The crystal structure of XdpB, the bacterial old yellow enzyme, in an FMN-free form." Plos One 13(4): e0195299.

• Zahradnik, J., J. Nunvar, H. Parizkova, L. Kolarova, A. Palyzova, H. Maresova, M. Grulich, E. Kyslikova and P. Kyslik (2018). "Agrobacterium bohemicum sp. nov. isolated from poppy seed wastes in central Bohemia." Syst Appl Microbiol 41(3): 184-190.

2017

• Cerny, J., B. Schneider and L. Biedermannova (2017). "WatAA: Atlas of Protein Hydration. Exploring synergies between data mining and ab initio calculations." Phys Chem Chem Phys 19(26): 17094-17102.

• Schneider, B., P. Bozikova, P. Cech, D. Svozil and J. Cerny (2017). "A DNA Structural Alphabet Distinguishes Structural Features of DNA Bound to Regulatory Proteins and in the Nucleosome Core Particle." Genes (Basel) 8(10).

2016

• Biedermannova, L. and B. Schneider (2016). "Hydration of proteins and nucleic acids: Advances in experiment and theory. A review." Biochim Biophys Acta 1860(9): 1821-1835.

• Cerny, J., P. Bozikova and B. Schneider (2016). "DNATCO: assignment of DNA conformers at dnatco.org." Nucleic Acids Research 44(W1): W284-287.

• Mikulecky, P., J. Zahradnik, P. Kolenko, J. Cerny, T. Charnavets, L. Kolarova, I. Necasova, P. N. Pham and B. Schneider (2016). "Crystal structure of human interferon-gamma receptor 2 reveals the structural basis for receptor specificity." Acta Crystallogr D Struct Biol 72(Pt 9): 1017-1025.

2015

• Biedermannova, L. and B. Schneider (2015). "Structure of the ordered hydration of amino acids in proteins: analysis of crystal structures." Acta Crystallogr D Biol Crystallogr 71(Pt 11): 2192-2202.

• Bockova, M., T. Springer, I. Necasova, J. Nunvar, B. Schneider and J. Homola (2015). "Monitoring RAYT activity by surface plasmon resonance biosensor." Anal Bioanal Chem 407(14): 3985-3993.

• Cerny, J., L. Biedermannova, P. Mikulecky, J. Zahradnik, T. Charnavets, P. Sebo and B. Schneider (2015). "Redesigning protein cavities as a strategy for increasing affinity in protein-protein interaction: interferon- gamma receptor 1 as a model." Biomed Research International 2015: 716945.

• Craveur, P., A. P. Joseph, J. Esque, T. J. Narwani, F. Noel, N. Shinada, M. Goguet, S. Leonard, P. Poulain, O. Bertrand, G. Faure, J. Rebehmed, A. Ghozlane, L. S. Swapna, R. M. Bhaskara, J. Barnoud, S. Teletchea, V. Jallu, J. Cerny, B. Schneider, C. Etchebest, N. Srinivasan, J. C. Gelly and A. G. de Brevern (2015). "Protein flexibility in the light of structural alphabets." Front Mol Biosci 2: 20.

• Charnavets, T., J. Nunvar, I. Necasova, J. Volker, K. J. Breslauer and B. Schneider (2015). "Conformational diversity of single-stranded DNA from bacterial repetitive extragenic palindromes: Implications for the DNA recognition elements of transposases." Biopolymers 103(10): 585-596.

2014

• Kuchar, M., L. Vankova, H. Petrokova, J. Cerny, R. Osicka, O. Pelak, H. Sipova, B. Schneider, J. Homola, P. Sebo, T. Kalina and P. Maly (2014). "Human interleukin-23 receptor antagonists derived from an albumin-binding domain scaffold inhibit IL-23-dependent ex vivo expansion of IL-17-producing T-cells." Proteins 82(6): 975-989.

• Nunvar, J., D. Elhottova, A. Chronakova, B. Schneider and I. Licha (2014). "Draft Genome Sequence of Stenotrophomonas maltophilia Strain 5BA-I-2, a Soil Isolate and a Member of a Phylogenetically Basal Lineage." Genome Announc 2(2).

• Schneider, B., J. Cerny, D. Svozil, P. Cech, J. C. Gelly and A. G. de Brevern (2014). "Bioinformatic analysis of the protein/DNA interface." Nucleic Acids Research 42(5): 3381-3394.

• Schneider, B., J. C. Gelly, A. G. de Brevern and J. Cerny (2014). "Local dynamics of proteins and DNA evaluated from crystallographic B factors." Acta Crystallogr D Biol Crystallogr 70(Pt 9): 2413-2419.

2013

• Cech, P., J. Kukal, J. Cerny, B. Schneider and D. Svozil (2013). "Automatic workflow for the classification of local DNA conformations." BMC Bioinformatics 14: 205.

• Kratochvilova, I., M. Vala, M. Weiter, M. Sperova, B. Schneider, O. Pav, J. Sebera, I. Rosenberg and V. Sychrovsky (2013). "Charge transfer through DNA/DNA duplexes and DNA/RNA hybrids: complex theoretical and experimental studies." Biophys Chem 180-181: 127-134.

• Mikulecky, P., J. Cerny, L. Biedermannova, H. Petrokova, M. Kuchar, J. Vondrasek, P. Maly, P. Sebo and B. Schneider (2013). "Increasing affinity of interferon-gamma receptor 1 to interferon-gamma by computer-aided design." Biomed Research International 2013: 752514.

• Nunvar, J., I. Licha and B. Schneider (2013). "Evolution of REP diversity: a comparative study." Bmc Genomics 14: 385.

2011

• Benda, L., B. Schneider and V. Sychrovsky (2011). "Calculating the response of NMR shielding tensor sigma(31P) and 2J(31P,13C) coupling constants in nucleic acid phosphate to coordination of the Mg2+ cation." J Phys Chem A 115(11): 2385-2395.

2010

• Joseph, A. P., G. Agarwal, S. Mahajan, J. C. Gelly, L. S. Swapna, B. Offmann, F. Cadet, A. Bornot, M. Tyagi, H. Valadie, B. Schneider, C. Etchebest, N. Srinivasan and A. G. De Brevern (2010). "A short survey on protein blocks." Biophys Rev 2(3): 137-147.

• Kratochvilova, I., T. Todorciuc, K. Kral, H. Nemec, M. Buncek, J. Sebera, S. Zalis, Z. Vokacova, V. Sychrovsky, L. Bednarova, P. Mojzes and B. Schneider (2010). "Charge transport in DNA oligonucleotides with various base-pairing patterns." J Phys Chem B 114(15): 5196-5205.

2009

• Vokacova, Z., M. Budesinsky, I. Rosenberg, B. Schneider, J. Sponer and V. Sychrovsky (2009). "Structure and dynamics of the ApA, ApC, CpA, and CpC RNA dinucleoside monophosphates resolved with NMR scalar spin-spin couplings." J Phys Chem B 113(4): 1182-1191.

CESNET Development Fund: 2024 – 0170, B. Schneider: Repository for "Life Sciences" Research Data. 2024

GAČR: GA24-11819S, G. F. Vives: Time-resolved vibrational spectroscopy of proteins assisted by genetically encoded non-canonical amino acids. 2024 – 2026

MŠMT: LX22NPO5102, B. Schneider: National institute for cancer research. 2022 – 2025

MŠMT: EF16_013/0001776, B. Schneider: Czech Infrastructure for Integrative Structural Biology for Human Health. 2017 – 2021

MŠMT: EF15_003/0000447, B. Schneider: Structural dynamics of biomolecular systems. 2016 – 2023

MEYS: LTAUSA18197, Schneider: Design, development, and testing of bioinformatic tools for validation of experimental and computer molecular models in structural biology, biotechnology and pharmacy. 2019-2022.

GACR: GA19-17398S, Schneider: De novo development of bivalent protein binders mimicking the function of interferons lambda. 2019-2021.

MEYS: LM2015047, Schneider: ELIXIR CZ: Czech national infrastructure for biological data. 2016-2019.

GACR: GA16-20507S, Schneider: Interleukins of the IL-10 family: specificity and targeted modulation of interactions with receptors. 2016-2018.

MEYS: CZ.1.07/2.3.00/30.0020, Schneider, Charnavets, Pavlínková, Dodd, Hejnalová: Biotechnological expert. 2012-2015.

GACR: GAP305/12/1801, Schneider: Molecular mechanisms of association of a novel type of transposase with repetitive palindromic elements. 2012-2014.

GACR: GPP205/12/P729, Biedermannová: Effect of protein hydration shell on the stability of protein complexes. 2012-2014.

GACR: GAP305/10/2184, Schneider: Structure-function relationships underlying protein-protein interactions. 2010-2014.

GACR: GAP302/10/0427, Vondrášek: Production and characterization of biologically active recombinant human ameloblastina hard tissue regeneration and differentiation inducing protein. 2010-2012.

MEYS: MEB021032, Schneider: Complex structural analysis of interaction at the protein – nucleic acid interface by unique bioinformatic descriptors. 2010-2011.