title: Mapping the distribution of packing topologies within protein interiors shows predominant preference for specific packing motifs.
abstract: BACKGROUND
  Mapping protein primary sequences to their three dimensional folds referred to as the 'second genetic code' remains an unsolved scientific problem. A crucial part of the problem concerns the geometrical specificity in side chain association leading to densely packed protein cores, a hallmark of correctly folded native structures. Thus, any model of packing within proteins should constitute an indispensable component of protein folding and design.
  
  
  RESULTS
  In this study an attempt has been made to find, characterize and classify recurring patterns in the packing of side chain atoms within a protein which sustains its native fold. The interaction of side chain atoms within the protein core has been represented as a contact network based on the surface complementarity and overlap between associating side chain surfaces. Some network topologies definitely appear to be preferred and they have been termed 'packing motifs', analogous to super secondary structures in proteins. Study of the distribution of these motifs reveals the ubiquitous presence of typical smaller graphs, which appear to get linked or coalesce to give larger graphs, reminiscent of the nucleation-condensation model in protein folding. One such frequently occurring motif, also envisaged as the unit of clustering, the three residue clique was invariably found in regions of dense packing. Finally, topological measures based on surface contact networks appeared to be effective in discriminating sequences native to a specific fold amongst a set of decoys.
  
  
  CONCLUSIONS
  Out of innumerable topological possibilities, only a finite number of specific packing motifs are actually realized in proteins. This small number of motifs could serve as a basis set in the construction of larger networks. Of these, the triplet clique exhibits distinct preference both in terms of composition and geometry.
authors: Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Bidhannagar, Kolkata, India.
authors: Sankar
authors: S
authors: Basu
authors: Dhananjay
authors: D
authors: Bhattacharyya
authors: Rahul
authors: R
authors: Banerjee
references: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W545-9
references: 20457744
references: BMC Bioinformatics. 2010 Mar 12;11:128
references: 20226048
references: PLoS Comput Biol. 2007 May;3(5):e94
references: 17530916
references: Trends Biochem Sci. 1995 Sep;20(9):374
references: 7482707
references: Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10869-73
references: 7479900
references: Protein Sci. 2002 Feb;11(2):322-31
references: 11790842
references: Protein Eng. 1994 Aug;7(8):969-76
references: 7809036
references: J Mol Biol. 1993 Dec 20;234(4):946-50
references: 8263940
references: J Mol Biol. 1977 May 25;112(3):535-42
references: 875032
references: J Mol Biol. 1987 Feb 20;193(4):775-91
references: 2441069
references: Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10383-8
references: 10984534
references: Phys Rev E Stat Nonlin Soft Matter Phys. 2002 Jun;65(6 Pt 1):061910
references: 12188762
references: Proteins. 2008 Jun;71(4):1899-907
references: 18175318
references: J Mol Biol. 1995 Apr 7;247(4):536-40
references: 7723011
references: J Mol Biol. 1999 Jan 29;285(4):1735-47
references: 9917408
references: Nature. 1998 Jun 4;393(6684):440-2
references: 9623998
references: Biophys J. 2004 Jan;86(1 Pt 1):85-91
references: 14695252
references: Biophys J. 2005 Dec;89(6):4159-70
references: 16150969
references: J Mol Biol. 2003 Oct 10;333(1):211-26
references: 14516754
references: J Biomol Struct Dyn. 2006 Apr;23(5):519-28
references: 16494501
references: Structure. 2008 Dec 10;16(12):1799-805
references: 19081056
references: J Mol Biol. 2004 Sep 10;342(2):651-64
references: 15327962
references: J Mol Biol. 2004 Dec 3;344(4):1135-46
references: 15544817
references: J Mol Biol. 1995 Jun 23;249(5):955-66
references: 7540695
references: Protein Sci. 2006 Nov;15(11):2507-24
references: 17075131
references: Proteins. 2008 Mar;70(4):1610-9
references: 18175329
references: Bioinformatics. 2007 Jul 15;23(14):1760-7
references: 17519248
references: J Mol Biol. 2005 May 6;348(3):507-12
references: 15826649
references: J Biol Chem. 1997 Jan 24;272(4):2031-4
references: 9036150
references: Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3747-52
references: 15007165
references: J Mol Biol. 2003 Jan 3;325(1):163-74
references: 12473459
references: J Phys Chem B. 1998 Apr 30;102(18):3586-616
references: 24889800
references: J Mol Biol. 2002 Aug 30;321(5):923-38
references: 12206771
references: Annu Rev Biophys Biomol Struct. 2006;35:49-65
references: 16689627
references: Protein Sci. 1994 Jul;3(7):997-1009
references: 7920265
references: Protein Eng. 1990 Mar;3(4):259-66
references: 2188263
references: J Mol Biol. 1995 Nov 24;254(2):260-88
references: 7490748
references: Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10172-7
references: 9294182
references: Nature. 2001 Feb 1;409(6820):641-5
references: 11214326
references: Genome Res. 2003 Nov;13(11):2498-504
references: 14597658
references: Protein Sci. 2002 Nov;11(11):2714-26
references: 12381853
references: Curr Opin Biotechnol. 1995 Aug;6(4):460-6
references: 7579657
references: J Mol Biol. 1999 Jul 2;290(1):305-18
references: 10388574
references: Biophys J. 2007 Jul 1;93(1):225-31
references: 17172302
references: J Mol Biol. 1992 Sep 5;227(1):227-38
references: 1522587
references: J Mol Biol. 2003 Dec 5;334(4):781-91
references: 14636602
references: Proc Natl Acad Sci U S A. 1992 May 1;89(9):4163-7
references: 1570343
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D393-5
references: 18948293
references: Protein Sci. 1997 Jun;6(6):1167-78
references: 9194177
references: J Mol Biol. 1974 Jan 5;82(1):1-14
references: 4818482
references: J Mol Biol. 1998 Apr 10;277(4):985-94
references: 9545386
references: J Mol Biol. 1993 Mar 20;230(2):543-74
references: 8464064
references: J Mol Biol. 1997 Nov 7;273(4):789-96
references: 9367772
references: Proteins. 2004 Feb 1;54(2):271-81
references: 14696189
references: Science. 2003 Nov 21;302(5649):1364-8
references: 14631033