Modeling of Protein–RNA Complex Structures Using Computational Docking Methods
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.
Key wordsProtein–RNA docking NPDock Molecular modeling Macromolecular complexes Structural bioinformatics Statistical potential
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.
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 26.The PyMOL Molecular Graphics System. The PyMOL Molecular Graphics System, vol Version 18.104.22.168. Schrödinger, LLC.Google Scholar