Pushing the limits of what is achievable in protein-DNA docking: benchmarking HADDOCK's performance.
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.
van Dijk
Marc
M
Bijvoet Center for Biomolecular Research, Science Faculty, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Bonvin
Alexandre M J J
AM
D019985:Benchmarking; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D012984:Software
D004268:DNA-Binding Proteins; D004247:DNA
Nucleic Acids Res. 2008 Aug;36(14):e88
18583363
Proteins. 2008 Sep;72(4):1114-24
18320590
J Biol Chem. 2000 Oct 6;275(40):31245-54
10906136
J Bone Miner Res. 1998 Mar;13(3):325-49
9525333
Nature. 1995 May 18;375(6528):203-11
7746322
Proteins. 2004 Oct 1;57(1):172-87
15326602
J Biol Chem. 1996 Aug 9;271(32):19464-74
8702636
Cell. 1984 Sep;38(2):361-9
6540625
J Steroid Biochem Mol Biol. 1996 Dec;59(5-6):377-88
9010343
Mol Cell Biol. 1991 Jan;11(1):564-7
1986247
J Mol Biol. 2000 Jul 21;300(4):877-87
10891275
J Mol Biol. 1998 Jul 17;280(3):345-53
9665841
Nucleic Acids Res. 2006 Jul 04;34(11):3317-25
16820531
Curr Opin Struct Biol. 2000 Aug;10(4):401-4
10981625
J Med Chem. 2004 Feb 12;47(4):821-8
14761184
Biochemistry. 2007 May 1;46(17):4943-50
17407261
Nature. 1998 Mar 12;392(6672):202-5
9515968
J Comput Chem. 2008 Nov 30;29(15):2582-92
18478582
Biochemistry. 2005 Oct 18;44(41):13500-9
16216073
Mol Cell Biol. 1991 May;11(5):2609-19
2017167
Nat Struct Biol. 1997 Sep;4(9):751-9
9303004
Nucleic Acids Res. 2008 Feb;36(3):756-69
18084026
Nat Protoc. 2008;3(7):1213-27
18600227
J Mol Biol. 1991 May 20;219(2):321-34
2038059
Genetics. 1987 Nov;117(3):429-35
3121434
J Mol Biol. 2007 Sep 28;372(4):992-1008
17692336
Curr Med Chem. 2004 Jan;11(1):91-107
14754428
Cell. 1989 Jun 30;57(7):1131-8
2500250
J Struct Biol. 2006 Mar;153(3):278-83
16427316
Proc Natl Acad Sci U S A. 2006 May 30;103(22):8384-9
16717183
ACS Chem Biol. 2006 Aug 22;1(7):451-60
17168523
Mol Cell Biol. 1989 Nov;9(11):4696-705
2689861
Nature. 1998 Jul 2;394(6688):96-101
9665136
Cell. 1989 Jun 30;57(7):1139-46
2500251
Nucleic Acids Res. 2003 Sep 1;31(17):5108-21
12930962
Nat Struct Biol. 1997 Sep;4(9):744-50
9303003
Proteins. 2002 Jun 1;47(4):409-43
12001221
J Mol Biol. 2000 Feb 18;296(2):509-20
10669605
J Mol Biol. 2007 Jun 1;369(2):474-88
17434531
Biophys Chem. 1988 Feb;29(1-2):31-7
3359001
Mol Cell Biol. 1989 Nov;9(11):4706-12
2689862
Curr Protein Pept Sci. 2008 Feb;9(1):1-15
18336319
Gene. 1998 Jan 5;206(1):11-21
9461409
Science. 1993 May 21;260(5111):1117-21
8388124
Mol Cell Biol. 1990 Jul;10(7):3386-96
2355911
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W235-9
19417072
J Comput Chem. 2003 Nov 30;24(15):1910-20
14515373
J Biol Chem. 2008 Feb 22;283(8):5158-67
18073212
Mol Cell Biol. 1993 Dec;13(12):7531-9
8246971
Nucleic Acids Res. 2007;35(17):5839-50
17720708
Pharmacol Ther. 1999 Nov;84(2):179-91
10596905
Nature. 1989 Mar 16;338(6212):271-4
2922054
Science. 1992 Aug 21;257(5073):1078-82
1509259
J Biol Chem. 1993 Nov 15;268(32):23812-7
8226917
Protein Eng. 1994 Jun;7(6):761-7
7937706
J Biomol Struct Dyn. 1989 Feb;6(4):627-34
2619931
Biochemistry. 2004 Aug 3;43(30):9600-9
15274614
J Mol Biol. 1993 Nov 20;234(2):446-62
8230225
Biochemistry. 2005 Mar 29;44(12):4794-804
15779906
J Biol Chem. 2008 Feb 15;283(7):4352-63
18073205
Endocr Rev. 1994 Jun;15(3):391-407
8076589
Protein Sci. 2005 Feb;14(2):278-83
15659362
Virology. 1990 Feb;174(2):557-75
2154890
Nucleic Acids Res. 1998 Jan 15;26(2):669-75
9421532
Proteins. 1996 Aug;25(4):486-500
8865343
Nature. 1994 Feb 24;367(6465):754-7
8107872
Proteins. 1998 Dec 1;33(4):535-49
9849937
Proteins. 2007 Dec 1;69(4):726-33
17803234
FEBS J. 2005 Jan;272(2):293-312
15654870
Mol Cell. 2007 Dec 14;28(5):708-14
18082595