title: Pushing the limits of what is achievable in protein-DNA docking: benchmarking HADDOCK's performance.
abstract: The intrinsic flexibility of DNA and the difficulty of identifying its interaction surface have long been challenges that prevented the development of efficient protein-DNA docking methods. We have demonstrated the ability our flexible data-driven docking method HADDOCK to deal with these before, by using custom-built DNA structural models. Here we put our method to the test on a set of 47 complexes from the protein-DNA docking benchmark. We show that HADDOCK is able to predict many of the specific DNA conformational changes required to assemble the interface(s). Our DNA analysis and modelling procedure captures the bend and twist motions occurring upon complex formation and uses these to generate custom-built DNA structural models, more closely resembling the bound form, for use in a second docking round. We achieve throughout the benchmark an overall success rate of 94% of one-star solutions or higher (interface root mean square deviation ≤4 A and fraction of native contacts >10%) according to CAPRI criteria. Our improved protocol successfully predicts even the challenging protein-DNA complexes in the benchmark. Finally, our method is the first to readily dock multiple molecules (N > 2) simultaneously, pushing the limits of what is currently achievable in the field of protein-DNA docking.
authors.affiliation: Bijvoet Center for Biomolecular Research, Science Faculty, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: van Dijk
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
mesh_terms: D019985:Benchmarking; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D012984:Software
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA
references.citation: Nucleic Acids Res. 2008 Aug;36(14):e88
references.pmid: 18583363
references.citation: Proteins. 2008 Sep;72(4):1114-24
references.pmid: 18320590
references.citation: J Biol Chem. 2000 Oct 6;275(40):31245-54
references.pmid: 10906136
references.citation: J Bone Miner Res. 1998 Mar;13(3):325-49
references.pmid: 9525333
references.citation: Nature. 1995 May 18;375(6528):203-11
references.pmid: 7746322
references.citation: Proteins. 2004 Oct 1;57(1):172-87
references.pmid: 15326602
references.citation: J Biol Chem. 1996 Aug 9;271(32):19464-74
references.pmid: 8702636
references.citation: Cell. 1984 Sep;38(2):361-9
references.pmid: 6540625
references.citation: J Steroid Biochem Mol Biol. 1996 Dec;59(5-6):377-88
references.pmid: 9010343
references.citation: Mol Cell Biol. 1991 Jan;11(1):564-7
references.pmid: 1986247
references.citation: J Mol Biol. 2000 Jul 21;300(4):877-87
references.pmid: 10891275
references.citation: J Mol Biol. 1998 Jul 17;280(3):345-53
references.pmid: 9665841
references.citation: Nucleic Acids Res. 2006 Jul 04;34(11):3317-25
references.pmid: 16820531
references.citation: Curr Opin Struct Biol. 2000 Aug;10(4):401-4
references.pmid: 10981625
references.citation: J Med Chem. 2004 Feb 12;47(4):821-8
references.pmid: 14761184
references.citation: Biochemistry. 2007 May 1;46(17):4943-50
references.pmid: 17407261
references.citation: Nature. 1998 Mar 12;392(6672):202-5
references.pmid: 9515968
references.citation: J Comput Chem. 2008 Nov 30;29(15):2582-92
references.pmid: 18478582
references.citation: Biochemistry. 2005 Oct 18;44(41):13500-9
references.pmid: 16216073
references.citation: Mol Cell Biol. 1991 May;11(5):2609-19
references.pmid: 2017167
references.citation: Nat Struct Biol. 1997 Sep;4(9):751-9
references.pmid: 9303004
references.citation: Nucleic Acids Res. 2008 Feb;36(3):756-69
references.pmid: 18084026
references.citation: Nat Protoc. 2008;3(7):1213-27
references.pmid: 18600227
references.citation: J Mol Biol. 1991 May 20;219(2):321-34
references.pmid: 2038059
references.citation: Genetics. 1987 Nov;117(3):429-35
references.pmid: 3121434
references.citation: J Mol Biol. 2007 Sep 28;372(4):992-1008
references.pmid: 17692336
references.citation: Curr Med Chem. 2004 Jan;11(1):91-107
references.pmid: 14754428
references.citation: Cell. 1989 Jun 30;57(7):1131-8
references.pmid: 2500250
references.citation: J Struct Biol. 2006 Mar;153(3):278-83
references.pmid: 16427316
references.citation: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8384-9
references.pmid: 16717183
references.citation: ACS Chem Biol. 2006 Aug 22;1(7):451-60
references.pmid: 17168523
references.citation: Mol Cell Biol. 1989 Nov;9(11):4696-705
references.pmid: 2689861
references.citation: Nature. 1998 Jul 2;394(6688):96-101
references.pmid: 9665136
references.citation: Cell. 1989 Jun 30;57(7):1139-46
references.pmid: 2500251
references.citation: Nucleic Acids Res. 2003 Sep 1;31(17):5108-21
references.pmid: 12930962
references.citation: Nat Struct Biol. 1997 Sep;4(9):744-50
references.pmid: 9303003
references.citation: Proteins. 2002 Jun 1;47(4):409-43
references.pmid: 12001221
references.citation: J Mol Biol. 2000 Feb 18;296(2):509-20
references.pmid: 10669605
references.citation: J Mol Biol. 2007 Jun 1;369(2):474-88
references.pmid: 17434531
references.citation: Biophys Chem. 1988 Feb;29(1-2):31-7
references.pmid: 3359001
references.citation: Mol Cell Biol. 1989 Nov;9(11):4706-12
references.pmid: 2689862
references.citation: Curr Protein Pept Sci. 2008 Feb;9(1):1-15
references.pmid: 18336319
references.citation: Gene. 1998 Jan 5;206(1):11-21
references.pmid: 9461409
references.citation: Science. 1993 May 21;260(5111):1117-21
references.pmid: 8388124
references.citation: Mol Cell Biol. 1990 Jul;10(7):3386-96
references.pmid: 2355911
references.citation: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W235-9
references.pmid: 19417072
references.citation: J Comput Chem. 2003 Nov 30;24(15):1910-20
references.pmid: 14515373
references.citation: J Biol Chem. 2008 Feb 22;283(8):5158-67
references.pmid: 18073212
references.citation: Mol Cell Biol. 1993 Dec;13(12):7531-9
references.pmid: 8246971
references.citation: Nucleic Acids Res. 2007;35(17):5839-50
references.pmid: 17720708
references.citation: Pharmacol Ther. 1999 Nov;84(2):179-91
references.pmid: 10596905
references.citation: Nature. 1989 Mar 16;338(6212):271-4
references.pmid: 2922054
references.citation: Science. 1992 Aug 21;257(5073):1078-82
references.pmid: 1509259
references.citation: J Biol Chem. 1993 Nov 15;268(32):23812-7
references.pmid: 8226917
references.citation: Protein Eng. 1994 Jun;7(6):761-7
references.pmid: 7937706
references.citation: J Biomol Struct Dyn. 1989 Feb;6(4):627-34
references.pmid: 2619931
references.citation: Biochemistry. 2004 Aug 3;43(30):9600-9
references.pmid: 15274614
references.citation: J Mol Biol. 1993 Nov 20;234(2):446-62
references.pmid: 8230225
references.citation: Biochemistry. 2005 Mar 29;44(12):4794-804
references.pmid: 15779906
references.citation: J Biol Chem. 2008 Feb 15;283(7):4352-63
references.pmid: 18073205
references.citation: Endocr Rev. 1994 Jun;15(3):391-407
references.pmid: 8076589
references.citation: Protein Sci. 2005 Feb;14(2):278-83
references.pmid: 15659362
references.citation: Virology. 1990 Feb;174(2):557-75
references.pmid: 2154890
references.citation: Nucleic Acids Res. 1998 Jan 15;26(2):669-75
references.pmid: 9421532
references.citation: Proteins. 1996 Aug;25(4):486-500
references.pmid: 8865343
references.citation: Nature. 1994 Feb 24;367(6465):754-7
references.pmid: 8107872
references.citation: Proteins. 1998 Dec 1;33(4):535-49
references.pmid: 9849937
references.citation: Proteins. 2007 Dec 1;69(4):726-33
references.pmid: 17803234
references.citation: FEBS J. 2005 Jan;272(2):293-312
references.pmid: 15654870
references.citation: Mol Cell. 2007 Dec 14;28(5):708-14
references.pmid: 18082595