Journal of Biomolecular NMR

, Volume 56, Issue 1, pp 51–63 | Cite as

Solvated protein–DNA docking using HADDOCK

  • Marc van Dijk
  • Koen M. Visscher
  • Panagiotis L. Kastritis
  • Alexandre M. J. J. Bonvin
Article

Abstract

Interfacial water molecules play an important role in many aspects of protein–DNA specificity and recognition. Yet they have been mostly neglected in the computational modeling of these complexes. We present here a solvated docking protocol that allows explicit inclusion of water molecules in the docking of protein–DNA complexes and demonstrate its feasibility on a benchmark of 30 high-resolution protein–DNA complexes containing crystallographically-determined water molecules at their interfaces. Our protocol is capable of reproducing the solvation pattern at the interface and recovers hydrogen-bonded water-mediated contacts in many of the benchmark cases. Solvated docking leads to an overall improvement in the quality of the generated protein–DNA models for cases with limited conformational change of the partners upon complex formation. The applicability of this approach is demonstrated on real cases by docking a representative set of 6 complexes using unbound protein coordinates, model-built DNA and knowledge-based restraints. As HADDOCK supports the inclusion of a variety of NMR restraints, solvated docking is also applicable for NMR-based structure calculations of protein–DNA complexes.

Keywords

Complexes Interface Water Protein DNA 

Notes

Acknowledgments

This work was supported by the Dutch Foundation for Scientific Research (NWO) through a VICI Grant (no 700.56.442) to A.M.J.J.B. and by the WeNMR project (European FP7 e-Infrastructure grant, contract no. 261572, www.wenmr.eu). The national Grid Initiatives of Belgium, France, Italy, Germany, The Netherlands (via the Dutch BiG Grid project), Portugal, Spain, UK, South Africa, Taiwan, and the Latin America GRID infrastructure via the Gisela project are acknowledged for the use of computing and storage facilities. The European Grid Initiative (www.egi.eu) is acknowledged for its support of the WeNMR Virtual Research Community.

Supplementary material

10858_2013_9734_MOESM1_ESM.pdf (78 kb)
Supplementary material 1 (PDF 78 kb)

References

  1. Ahmad M, Gu W, Geyer T, Helms V (2011) Adhesive water networks facilitate binding of protein interfaces. Nat Commun 2:261. doi: 10.1038/ncomms1258 CrossRefGoogle Scholar
  2. Aloy P, Russell RB (2006) Structural systems biology: modelling protein interactions. Nat Rev Mol Cell Biol 7:188–197. doi: 10.1038/nrm1859 CrossRefGoogle Scholar
  3. Baker D, Sali A (2001) Protein structure prediction and structural genomics. Sci Signal 294:93–96. doi: 10.1126/science.1065659 Google Scholar
  4. Ball P (2008) Water as an active constituent in cell biology. Chem Rev 108:74–108. doi: 10.1021/cr068037a CrossRefGoogle Scholar
  5. Berman H, Henrick K, Nakamura H, Markley JL (2007) The worldwide Protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data. Nucleic Acids Res 35:D301–D303. doi: 10.1093/nar/gkl971 CrossRefGoogle Scholar
  6. Brunger AT (2007) Version 1.2 of the crystallography and NMR system. Nat Protoc 2:2728–2733. doi: 10.1038/nprot.2007.406 CrossRefGoogle Scholar
  7. Chen L, Wang K, Shao Y et al (2008) Structural insight into the mechanisms of Wnt signaling antagonism by Dkk. J Biol Chem 283:23364–23370. doi: 10.1074/jbc.M802375200 CrossRefGoogle Scholar
  8. Clore GM (2011) Exploring translocation of proteins on DNA by NMR. J Biomol NMR 51:209–219. doi: 10.1007/s10858-011-9555-8 CrossRefGoogle Scholar
  9. Collins FS, Green ED, Guttmacher AE, Guyer MS (2003) A vision for the future of genomics research. Nature 422:835–847. doi: 10.1038/nature01626 ADSCrossRefGoogle Scholar
  10. Collura V, Boissy G (2007) From protein-protein complexes to interactomics. In: Bertrand E, Faupel M (eds) Subcellular biochemistry, vol 43. pp 135–183 Google Scholar
  11. Cusick ME, Klitgord N, Vidal M, Hill DE (2005) Interactome: gateway into systems biology. Hum Mol Genet 14(Spec No. 2):R171–R181. doi: 10.1093/hmg/ddi335 Google Scholar
  12. de Vries SJ, van Dijk ADJ, Krzeminski M et al (2007) HADDOCK versus HADDOCK: new features and performance of HADDOCK2.0 on the CAPRI targets. Proteins Struct Funct Bioinform 69:726–733. doi: 10.1002/prot.21723 CrossRefGoogle Scholar
  13. Dominguez C, Boelens R, Bonvin AMJJ (2003) HADDOCK: a protein–protein docking approach based on biochemical or biophysical information. J Am Chem Soc 125:1731–1737. doi: 10.1021/ja026939x CrossRefGoogle Scholar
  14. Dunitz JD (1994) The entropic cost of bound water in crystals and biomolecules. Science 264:670. doi: 10.1126/science.264.5159.670 ADSCrossRefGoogle Scholar
  15. Dunn RK, Kingston RE (2007) Gene regulation in the postgenomic era: technology takes the wheel. Mol Cell 28:708–714. doi: 10.1016/j.molcel.2007.11.022 CrossRefGoogle Scholar
  16. Fernández-Recio J, Totrov M, Abagyan R (2004) Identification of protein–protein interaction sites from docking energy landscapes. J Mol Biol 335:843–865CrossRefGoogle Scholar
  17. Giudice E, Lavery R (2002) Simulations of nucleic acids and their complexes. Acc Chem Res 35:350–357CrossRefGoogle Scholar
  18. Horton NC (1998) Recognition of flanking DNA sequences by EcoRV endonuclease involves alternative patterns of water-mediated contacts. J Biol Chem 273:21721–21729. doi: 10.1074/jbc.273.34.21721 CrossRefGoogle Scholar
  19. Huang N, Shoichet BK (2008) Exploiting ordered waters in molecular docking. J Med Chem 51:4862–4865. doi: 10.1021/jm8006239 CrossRefGoogle Scholar
  20. Hubbard SJ, Thornton JM (1993) NACCESS computer program. Department of Biochemistry and Molecular Biology, University College LondonGoogle Scholar
  21. Hummer G, García AE, Soumpasis DM (1995) Hydration of nucleic acid fragments: comparison of theory and experiment for high-resolution crystal structures of RNA, DNA, and DNA–drug complexes. Biophys J 68:1639–1652. doi: 10.1016/S0006-3495(95)80381-4 CrossRefGoogle Scholar
  22. Janin J (1999) Wet and dry interfaces: the role of solvent in protein–protein and protein–DNA recognition. Structure 7:R277–R279CrossRefGoogle Scholar
  23. Jayaram B, Jain T (2004) The role of water in protein–DNA recognition. Annu Rev Biophys Biomol Struct 33:343–361. doi: 10.1146/annurev.biophys.33.110502.140414 CrossRefGoogle Scholar
  24. Jones S, van Heyningen P, Berman HM, Thornton JM (1999) Protein–DNA interactions: a structural analysis. J Mol Biol 287:877–896. doi: 10.1006/jmbi.1999.2659 CrossRefGoogle Scholar
  25. Joosten RP, Joosten K, Murshudov GN, Perrakis A (2012) PDB_REDO: constructive validation, more than just looking for errors. Acta Crystallogr D Biol Crystallogr 68:484–496. doi: 10.1107/S0907444911054515 CrossRefGoogle Scholar
  26. Jorgensen WL, Chandrasekhar J, Madura JD (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926–935. doi: 10.1063/1.445869 ADSCrossRefGoogle Scholar
  27. Kalodimos CG, Biris N, Bonvin AMJJ et al (2004) Structure and flexibility adaptation in nonspecific and specific protein–DNA complexes. Science 305:386–389. doi: 10.1126/science.1097064 ADSCrossRefGoogle Scholar
  28. Kastritis PL, van Dijk ADJ, Bonvin AMJJ (2012a) Explicit treatment of water molecules in data-driven protein–protein docking: the solvated HADDOCKing approach. Methods Mol Biol 819:355–374. doi: 10.1007/978-1-61779-465-0_22 CrossRefGoogle Scholar
  29. Kastritis PL, Visscher KM, van Dijk ADJ, Bonvin AMJJ (2012b) Solvated protein–protein docking using kyte–doolittle-based water preferences. Proteins Struct Funct Bioinform. doi: 10.1002/prot.24210 Google Scholar
  30. Lensink MF, Wodak SJ (2010a) Blind predictions of protein interfaces by docking calculations in CAPRI. Proteins Struct Funct Bioinform 78:3085–3095. doi: 10.1002/prot.22850 CrossRefGoogle Scholar
  31. Lensink MF, Wodak SJ (2010b) Docking and scoring protein interactions: CAPRI 2009. Proteins Struct Funct Bioinform 78:3073–3084. doi: 10.1002/prot.22818 CrossRefGoogle Scholar
  32. Li Z, Lazaridis T (2007) Water at biomolecular binding interfaces. Phys Chem Chem Phys 9:573–581. doi: 10.1039/b612449f CrossRefGoogle Scholar
  33. Liu LA, Bradley P (2012) Atomistic modeling of protein–DNA interaction specificity: progress and applications. Curr Opin Struct Biol 22:397–405. doi: 10.1016/j.sbi.2012.06.002 CrossRefGoogle Scholar
  34. Liu P, Agrafiotis DK, Theobald DL (2010) Fast determination of the optimal rotational matrix for macromolecular superpositions. J Comput Chem 1561–1563. doi: 10.1002/jcc.21439
  35. Luscombe NM, Laskowski RA, Thornton JM (1997) NUCPLOT: a program to generate schematic diagrams of protein-nucleic acid interactions. Nucleic Acids Res 25:4940–4945. doi: 10.1093/nar/29.13.2860 CrossRefGoogle Scholar
  36. Luscombe NM, Austin SE, Berman HM, Thornton JM (2000) An overview of the structures of protein–DNA complexes. Genome Biol 1:1–10. doi: 10.1186/gb-2000-1-1-reviews001 CrossRefGoogle Scholar
  37. Luscombe NM, Laskowski RA, Thornton JM (2001) Amino acid–base interactions: a three-dimensional analysis of protein–DNA interactions at an atomic level. Nucleic Acids Res 29:2860–2874CrossRefGoogle Scholar
  38. Makarov V, Pettitt BM, Feig M (2002) Solvation and hydration of proteins and nucleic acids: a theoretical view of simulation and experiment. Acc Chem Res 35:376–384CrossRefGoogle Scholar
  39. Marabotti A, Spyrakis F, Facchiano A et al (2008) Energy-based prediction of amino acid–nucleotide base recognition. J Comput Chem 29:1955–1969. doi: 10.1002/jcc.20954 CrossRefGoogle Scholar
  40. Melquiond AS, Karaca E, Kastritis PL, Bonvin AM (2011) Next challenges in protein–protein docking: from proteome to interactome and beyond. WIREs Comput Mol Sci 642–651. doi: 10.1002/wcms.91
  41. Moitessier N, Westhof E, Hanessian S (2006) Docking of aminoglycosides to hydrated and flexible RNA. J Med Chem 49:1023–1033. doi: 10.1021/jm0508437 CrossRefGoogle Scholar
  42. Nadassy K, Wodak SJ, Janin J (1999) Structural features of protein–nucleic acid recognition sites. Biochemistry 38:1999–2017. doi: 10.1021/bi982362d CrossRefGoogle Scholar
  43. Nederveen AJ, Doreleijers JF, Vranken W et al (2005) RECOORD: a recalculated coordinate database of 500+ proteins from the PDB using restraints from the BioMagResBank. Proteins Struct Funct Bioinform 59:662–672. doi: 10.1002/prot.20408 CrossRefGoogle Scholar
  44. Otwinowski Z, Schevitz RW, Zhang RG et al (1988) Crystal structure of trp repressor/operator complex at atomic resolution. Nature 335:321–329. doi: 10.1038/335321a0 ADSCrossRefGoogle Scholar
  45. Pakotiprapha D, Jeruzalmi D (2009) Crystallization of protein–DNA complexes. Encycl Life Sci (ELS). doi: 10.1002/9780470015902.a0002720.pub2 Google Scholar
  46. Pandey A, Mann M (2000) Proteomics to study genes and genomes. Nature 405:837–846. doi: 10.1038/35015709 CrossRefGoogle Scholar
  47. Pérez A, Luque FJ, Orozco M (2012) Frontiers in molecular dynamics simulations of DNA. Acc Chem Res 45:196–205. doi: 10.1021/ar2001217 CrossRefGoogle Scholar
  48. Reddy CK, Das A, Jayaram B (2001) Do water molecules mediate protein–DNA recognition? J Mol Biol 314:619–632. doi: 10.1006/jmbi.2001.5154 CrossRefGoogle Scholar
  49. Renuse S, Chaerkady R, Pandey A (2011) Proteogenomics. Proteomics 11:620–630. doi: 10.1002/pmic.201000615 CrossRefGoogle Scholar
  50. Roberts VA, Case DA, Tsui V (2004) Predicting interactions of winged-helix transcription factors with DNA. Proteins Struct Funct Bioinform 57:172–187. doi: 10.1002/prot.20193 CrossRefGoogle Scholar
  51. Rodrigues JPGLM, Trellet M, Schmitz C et al (2012) Clustering biomolecular complexes by residue contacts similarity. Proteins Struct Funct Bioinform 80:1810–1817. doi: 10.1002/prot.24078 Google Scholar
  52. Samish I (2009) Search and sampling in structural bioinformatics. In: Gu J, Bourne PE (eds) Structural bioinformatics. Wiley, Hoboken, pp 207–235Google Scholar
  53. Schneider B, Cohen D, Berman HM (1992) Hydration of DNA bases: analysis of crystallographic data. Biopolymers 32:725–750. doi: 10.1002/bip.360320703 CrossRefGoogle Scholar
  54. Schwabe JW (1997) The role of water in protein–DNA interactions. Curr Opin Struct Biol 7:126–134CrossRefGoogle Scholar
  55. Shakked Z, Guzikevich-Guerstein G, Frolow F et al (1994) Determinants of repressor/operator recognition from the structure of the trp operator binding site. Nature 368:469–473. doi: 10.1038/368469a0 ADSCrossRefGoogle Scholar
  56. Sidorova NY, Rau DC (1996) Differences in water release for the binding of EcoRI to specific and nonspecific DNA sequences. Proc Natl Acad Sci USA 93:12272–12277ADSCrossRefGoogle Scholar
  57. Spyrakis F, Cozzini P, Bertoli C et al (2007) Energetics of the protein–DNA–water interaction. BMC Struct Biol 7:4. doi: 10.1186/1472-6807-7-4 CrossRefGoogle Scholar
  58. Theobald DL (2005) Rapid calculation of RMSDs using a quaternion-based characteristic polynomial. Acta Crystallogr A Found Crystallogr 61:478–480. doi: 10.1107/S0108767305015266 ADSCrossRefGoogle Scholar
  59. van Dijk ADJ, Bonvin AMJJ (2006) Solvated docking: introducing water into the modelling of biomolecular complexes. Bioinformatics 22:2340–2347. doi: 10.1093/bioinformatics/btl395 CrossRefGoogle Scholar
  60. van Dijk M, Bonvin AMJJ (2008) A protein–DNA docking benchmark. Nucleic Acids Res 36:e88. doi: 10.1093/nar/gkn386 CrossRefGoogle Scholar
  61. van Dijk M, Bonvin AMJJ (2009) 3D-DART: a DNA structure modelling server. Nucleic Acids Res 37:W235–W239. doi: 10.1093/nar/gkp287 CrossRefGoogle Scholar
  62. van Dijk M, Bonvin AMJJ (2010) Pushing the limits of what is achievable in protein–DNA docking: benchmarking HADDOCK’s performance. Nucleic Acids Res 38:5634–5647. doi: 10.1093/nar/gkq222 CrossRefGoogle Scholar
  63. van Dijk ADJ, Boelens R, Bonvin AMJJ (2005) Data-driven docking for the study of biomolecular complexes. FEBS J 272:293–312. doi: 10.1111/j.1742-4658.2004.04473.x CrossRefGoogle Scholar
  64. van Dijk M, van Dijk ADJ, Hsu V et al (2006) Information-driven protein–DNA docking using HADDOCK: it is a matter of flexibility. Nucleic Acids Res 34:3317–3325. doi: 10.1093/nar/gkl412 CrossRefGoogle Scholar
  65. Varani G, Chen Y, Leeper TC (2004) NMR studies of protein–nucleic acid interactions. Methods Mol Biol 278:289–312. doi: 10.1385/1-59259-809-9:289 Google Scholar
  66. Virtanen JJ, Makowski L, Sosnick TR, Freed KF (2010) Modeling the hydration layer around proteins: HyPred. Biophys J 99:1611–1619. doi: 10.1016/j.bpj.2010.06.027 CrossRefGoogle Scholar
  67. Zhang J, Chiodini R, Badr A, Zhang G (2011) The impact of next-generation sequencing on genomics. J Genet Genomics 38:95–109. doi: 10.1016/j.jgg.2011.02.003 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Marc van Dijk
    • 1
  • Koen M. Visscher
    • 1
  • Panagiotis L. Kastritis
    • 1
  • Alexandre M. J. J. Bonvin
    • 1
  1. 1.Bijvoet Center for Biomolecular Research, Faculty of Science-ChemistryUtrecht UniversityUtrechtThe Netherlands

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