M-ORBIS: mapping of molecular binding sites and surfaces.
M-ORBIS is a Molecular Cartography approach that performs integrative high-throughput analysis of structural data to localize all types of binding sites and associated partners by homology and to characterize their properties and behaviors in a systemic way. The robustness of our binding site inferences was compared to four curated datasets corresponding to protein heterodimers and homodimers and protein-DNA/RNA assemblies. The Molecular Cartographies of structurally well-detailed proteins shows that 44% of their surfaces interact with non-solvent partners. Residue contact frequencies with water suggest that ∼86% of their surfaces are transiently solvated, whereas only 15% are specifically solvated. Our analysis also reveals the existence of two major binding site families: specific binding sites which can only bind one type of molecule (protein, DNA, RNA, etc.) and polyvalent binding sites that can bind several distinct types of molecule. Specific homodimer binding sites are for instance nearly twice as hydrophobic than previously described and more closely resemble the protein core, while polyvalent binding sites able to form homo and heterodimers more closely resemble the surfaces involved in crystal packing. Similarly, the regions able to bind DNA and to alternatively form homodimers, are more hydrophobic and less polar than previously described DNA binding sites.
Albou
Laurent-Philippe
LP
Department of Biology and Structural Genomics, IGBMC, Illkirch, France.
Poch
Olivier
O
Moras
Dino
D
D001665:Binding Sites; D019295:Computational Biology; D019281:Dimerization; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry; D014867:Water / Q000737:chemistry
D011506:Proteins; D014867:Water
J Mol Biol. 1998 Apr 17;277(5):1111-28
9571026
Proteins. 2008 Feb 1;70(2):363-77
17680687
Bioinformatics. 2008 Mar 1;24(5):652-8
18204058
J Mol Model. 2007 Jul;13(6-7):665-75
17394030
Nat Struct Biol. 1997 Dec;4(12):973-4
9406542
Protein Eng. 1998 Sep;11(9):739-47
9796821
Q Rev Biophys. 2008 May;41(2):133-80
18812015
Proteins. 2009 Jul;76(1):1-12
19089982
Curr Opin Chem Biol. 2004 Feb;8(1):3-7
15036149
Nucleic Acids Res. 2009 Jan;37(Database issue):D360-4
18836195
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):13-20
8552589
J Mol Biol. 1998 Jul 3;280(1):1-9
9653027
Biochemistry. 1999 Feb 16;38(7):1999-2017
10026283
EMBO Rep. 2004 Apr;5(4):423-9
15105832
Proteins. 2000 Oct 1;41(1):47-57
10944393
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915-9
1438297
Nucleic Acids Res. 2003 Jul 1;31(13):3829-32
12824430
Bioinformatics. 2007 Dec 1;23(23):3131-8
17933849
Trends Biochem Sci. 1998 Sep;23(9):358-61
9787643
Nature. 1995 Jul 27;376(6538):313-20
7630397
Proteins. 2008 Nov 15;73(3):705-9
18491384
Bioinformatics. 2007 May 15;23(10):1282-8
17379688
Curr Opin Struct Biol. 2006 Apr;16(2):152-9
16546375
Nucleic Acids Res. 2008 May;36(8):2705-16
18353859
J Mol Biol. 1999 Feb 5;285(5):2177-98
9925793
Mol Cell. 2000 Feb;5(2):289-98
10882070
EMBO J. 2004 May 19;23(10):2083-91
15103326
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D154-9
15608167
BMC Bioinformatics. 2006 Jan 19;7:27
16423290
Proteins. 2005 Jul 1;60(1):36-45
15856483
Curr Opin Struct Biol. 1995 Feb;5(1):103-13
7773739
J Mol Biol. 2007 Sep 21;372(3):774-97
17681537
Proteins. 2007 Feb 15;66(3):630-45
17152079
J Mol Biol. 2004 Feb 27;336(4):943-55
15095871
Proteins. 2002 May 15;47(3):334-43
11948787
Acta Crystallogr D Biol Crystallogr. 2002 Jun;58(Pt 6  No 1):899-907
12037327
Nature. 1993 Jun 17;363(6430):595-602
8510751
Proteins. 2009 Aug 15;76(3):527-35
19425109
Proteins. 2003 Nov 15;53(3):708-19
14579361
PLoS Comput Biol. 2009 Mar;5(3):e1000335
19325869
Proteins. 2008 Sep;72(4):1259-73
18361455
Methods Biochem Anal. 2003;44:387-407
12647396
Proteins. 2006 Mar 15;62(3):630-40
16329107