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Modeling of Protein–RNA Complex Structures Using Computational Docking Methods

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Computational Design of Ligand Binding Proteins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1414))

Abstract

A significant part of biology involves the formation of RNA–protein complexes. X-ray crystallography has added a few solved RNA–protein complexes to the repertoire; however, it remains challenging to capture these complexes and often only the unbound structures are available. This has inspired a growing interest in finding ways to predict these RNA–protein complexes. In this study, we show ways to approach this problem by computational docking methods, either with a fully automated NPDock server or with a workflow of methods for generation of many alternative structures followed by selection of the most likely solution. We show that by introducing experimental information, the structure of the bound complex is rendered far more likely to be within reach. This study is meant to help the user of docking software understand how to grapple with a typical realistic problem in RNA–protein docking, understand what to expect in the way of difficulties, and recognize the current limitations.

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References

  1. Moller W, Amons R, Groene JC, Garrett RA, Terhorst CP (1969) Protein-ribonucleic acid interactions in ribosomes. Biochim Biophys Acta 190(2):381–390

    Article  CAS  PubMed  Google Scholar 

  2. Demeshkina N, Jenner L, Yusupova G, Yusupov M (2010) Interactions of the ribosome with mRNA and tRNA. Curr Opin Struct Biol 20(3):325–332. doi:10.1016/j.sbi.2010.03.002

    Article  CAS  PubMed  Google Scholar 

  3. Ghildiyal M, Zamore PD (2009) Small silencing RNAs: an expanding universe. Nat Rev Genet 10(2):94–108, nrg2504 (pii)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pichon C, Felden B (2007) Proteins that interact with bacterial small RNA regulators. FEMS Microbiol Rev 31(5):614–625, FMR079 (pii)

    Article  CAS  PubMed  Google Scholar 

  5. Hoskins AA, Moore MJ (2012) The spliceosome: a flexible, reversible macromolecular machine. Trends Biochem Sci 37(5):179–188. doi:10.1016/j.tibs.2012.02.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Doudna JA (2000) Structural genomics of RNA. Nat Struct Biol 7(Suppl):954–956

    Article  CAS  PubMed  Google Scholar 

  7. Ke A, Doudna JA (2004) Crystallization of RNA and RNA-protein complexes. Methods 34(3):408–414

    Article  CAS  PubMed  Google Scholar 

  8. Tuszynska I, Matelska D, Magnus M, Chojnowski G, Kasprzak JM, Kozlowski LP, Dunin-Horkawicz S, Bujnicki JM (2014) Computational modeling of protein-RNA complex structures. Methods 65(3):310–319. doi:10.1016/j.ymeth.2013.09.014

    Article  CAS  PubMed  Google Scholar 

  9. Whitford PC, Ahmed A, Yu Y, Hennelly SP, Tama F, Spahn CM, Onuchic JN, Sanbonmatsu KY (2011) Excited states of ribosome translocation revealed through integrative molecular modeling. Proc Natl Acad Sci U S A 108(47):18943–18948. doi:10.1073/pnas.1108363108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gan HH, Gunsalus KC (2013) Tertiary structure-based analysis of microRNA-target interactions. RNA 19:539. doi:10.1261/rna.035691.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Anokhina M, Bessonov S, Miao Z, Westhof E, Hartmuth K, Luhrmann R (2013) RNA structure analysis of human spliceosomes reveals a compact 3D arrangement of snRNAs at the catalytic core. EMBO J 32(21):2804–2818. doi:10.1038/emboj.2013.198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cheng LT, Wang Z, Setny P, Dzubiella J, Li B, McCammon JA (2009) Interfaces and hydrophobic interactions in receptor-ligand systems: a level-set variational implicit solvent approach. J Chem Phys 131(14):144102. doi:10.1063/1.3242274

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hoang C, Ferre-D’Amare AR (2001) Cocrystal structure of a tRNA Psi55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme. Cell 107(7):929–939

    Article  CAS  PubMed  Google Scholar 

  14. Ruff M, Krishnaswamy S, Boeglin M, Poterszman A, Mitschler A, Podjarny A, Rees B, Thierry JC, Moras D (1991) Class II aminoacyl transfer RNA synthetases: crystal structure of yeast aspartyl-tRNA synthetase complexed with tRNA(Asp). Science 252(5013):1682–1689

    Article  CAS  PubMed  Google Scholar 

  15. Rose PW, Prlic A, Bi C, Bluhm WF, Christie CH, Dutta S, Green RK, Goodsell DS, Westbrook JD, Woo J, Young J, Zardecki C, Berman HM, Bourne PE, Burley SK (2015) The RCSB protein data bank: views of structural biology for basic and applied research and education. Nucleic Acids Res 43(Database issue):D345–D356. doi:10.1093/nar/gku1214

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sauter C, Lorber B, Cavarelli J, Moras D, Giege R (2000) The free yeast aspartyl-tRNA synthetase differs from the tRNA(Asp)-complexed enzyme by structural changes in the catalytic site, hinge region, and anticodon-binding domain. J Mol Biol 299(5):1313–1324

    Article  CAS  PubMed  Google Scholar 

  17. Westhof E, Dumas P, Moras D (1988) Restrained refinement of two crystalline forms of yeast aspartic acid and phenylalanine transfer RNA crystals. Acta Crystallogr A 44(Pt 2):112–123

    Article  PubMed  Google Scholar 

  18. Rother M, Rother K, Puton T, Bujnicki JM (2011) ModeRNA: a tool for comparative modeling of RNA 3D structure. Nucleic Acids Res 39(10):4007–4022. doi:10.1093/nar/gkq1320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cock PJ, Antao T, Chang JT, Chapman BA, Cox CJ, Dalke A, Friedberg I, Hamelryck T, Kauff F, Wilczynski B, de Hoon MJ (2009) Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 25(11):1422–1423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rother M, Milanowska K, Puton T, Jeleniewicz J, Rother K, Bujnicki JM (2011) ModeRNA server: an online tool for modeling RNA 3D structures. Bioinformatics 27(17):2441–2442

    Article  CAS  PubMed  Google Scholar 

  21. Katchalski-Katzir E, Shariv I, Eisenstein M, Friesem AA, Aflalo C, Vakser IA (1992) Molecular surface recognition: determination of geometric fit between proteins and their ligands by correlation techniques. Proc Natl Acad Sci U S A 89(6):2195–2199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gajda MJ, Tuszynska I, Kaczor M, Bakulina AY, Bujnicki JM (2010) FILTREST3D: discrimination of structural models using restraints from experimental data. Bioinformatics 26(23):2986–2987, btq582 (pii)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Frishman D, Argos P (1995) Knowledge-based protein secondary structure assignment. Proteins 23(4):566–579

    Article  CAS  PubMed  Google Scholar 

  24. Tuszynska I, Bujnicki JM (2011) DARS-RNP and QUASI-RNP: new statistical potentials for protein-RNA docking. BMC Bioinform 12(1):348, 1471-2105-12-348 (pii)

    Article  CAS  Google Scholar 

  25. Tuszynska I, Magnus M, Jonak K, Dawson W, Bujnicki JM (2015) NPDock: a web server for protein-nucleic acid docking. Nucleic Acids Res 43:W425. doi:10.1093/nar/gkv493

    Article  PubMed  PubMed Central  Google Scholar 

  26. The PyMOL Molecular Graphics System. The PyMOL Molecular Graphics System, vol Version 1.5.0.4. Schrödinger, LLC.

    Google Scholar 

  27. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612

    Article  CAS  PubMed  Google Scholar 

  28. Shortle D, Simons KT, Baker D (1998) Clustering of low-energy conformations near the native structures of small proteins. Proc Natl Acad Sci U S A 95(19):11158–11162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ditzler MA, Otyepka M, Sponer J, Walter NG (2010) Molecular dynamics and quantum mechanics of RNA: conformational and chemical change we can believe in. Acc Chem Res 43(1):40–47. doi:10.1021/ar900093g

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Estarellas C, Otyepka M, Koča J, Banáš P, Krepl M, Šponer J (2015) Molecular dynamic simulations of protein/RNA complexes: CRISPR/Csy4 endoribonuclease. Biochim Biophys Acta 1850:1072–1090. doi:10.1016/j.bbagen.2014.10.021

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the European Commission (E.C. REGPOT grant FishMed, contract number 316125, to Jacek Kuźnicki in IIMCB) and by the European Research Council (ERC, StG grant RNA + P = 123D grant to J.M.B). J.M.B was also supported by the “Ideas for Poland” fellowship from the Foundation for Polish Science. J.M.K., I.T., and M.M. were additionally supported by the Polish National Science Center (NCN, grants 2012/05/N/NZ2/01652 to J.M.K., 2011/03/N/NZ2/03241 to I.T., and 2014/12/T/NZ2/00501 to M.M.). The development and maintenance of computational servers was funded by the E.C. structural funds (grant POIG.02.03.00–00–003/09 to J.M.B.). Calculations were performed on a high-performance computing cluster at IIMCB, Warsaw (supported by IIMCB statutory funds). The authors are grateful to Stanisław Dunin-Horkawicz and Michał Boniecki for useful discussions and comments on the manuscript.

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Authors and Affiliations

  1. Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology in Warsaw, ul. Ks. Trojdena 4, 02-109, Warsaw, Poland

    Bharat Madan, Joanna M. Kasprzak, Irina Tuszynska, Marcin Magnus, Krzysztof Szczepaniak, Wayne K. Dawson & Janusz M. Bujnicki

  2. Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, ul. Umultowska 89, 61-614, Poznan, Poland

    Joanna M. Kasprzak & Janusz M. Bujnicki

  3. Institute of Informatics, University of Warsaw, ul. Banacha 2, 02-097, Warsaw, Poland

    Irina Tuszynska

Authors
  1. Bharat Madan
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  2. Joanna M. Kasprzak
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  3. Irina Tuszynska
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  4. Marcin Magnus
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  5. Krzysztof Szczepaniak
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  6. Wayne K. Dawson
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  7. Janusz M. Bujnicki
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Corresponding author

Correspondence to Janusz M. Bujnicki .

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Editors and Affiliations

  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Cen, Seattle, Washington, USA

    Barry L. Stoddard

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Madan, B. et al. (2016). Modeling of Protein–RNA Complex Structures Using Computational Docking Methods. In: Stoddard, B. (eds) Computational Design of Ligand Binding Proteins. Methods in Molecular Biology, vol 1414. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3569-7_21

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  • DOI: https://doi.org/10.1007/978-1-4939-3569-7_21

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3567-3

  • Online ISBN: 978-1-4939-3569-7

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