title: The protein meta-structure: a novel concept for chemical and molecular biology.
abstract: The ultimate goal of bioinformatics or computational chemical biology is the sequence-based prediction of protein functionality. However, due to the degeneracy of the primary sequence code there is no unambiguous relationship. The degeneracy can be partly lifted by going to higher levels of abstraction and, for example, incorporating 3D structural information. However, sometimes even at this conceptual level functional ambiguities often remain. Here a novel conceptual framework is described (the protein meta-structure). At this level of abstraction, the protein structure is viewed as an intricate network of interacting residues. This novel conception offers unique possibilities for chemical (molecular) biology, structural genomics and drug discovery. In this review some prototypical applications will be presented that serve to illustrate the potential of the methodology.
authors.affiliation: Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter Campus 5, 1030, Vienna, Austria. robert.konrat@univie.ac.at
authors.forename: Robert
authors.initials: R
authors.lastname: Konrat
mesh_terms: D000818:Animals; D056246:Chemistry, Analytic; D019295:Computational Biology / Q000379:methods / Q000639:trends; D003210:Concept Formation; D006801:Humans; D008958:Models, Molecular; D008967:Molecular Biology / Q000379:methods; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins
references.citation: Curr Opin Struct Biol. 2005 Feb;15(1):35-41
references.pmid: 15718131
references.citation: Annu Rev Pharmacol Toxicol. 2001;41:723-49
references.pmid: 11264474
references.citation: Genome Inform Ser Workshop Genome Inform. 1999;10:30-40
references.pmid: 11072340
references.citation: Annu Rev Biochem. 2001;70:209-46
references.pmid: 11395407
references.citation: Science. 1998 Dec 11;282(5396):2022-8
references.pmid: 9851918
references.citation: Curr Opin Struct Biol. 2006 Jun;16(3):393-8
references.pmid: 16678402
references.citation: Chem Rev. 2004 Aug;104(8):3607-22
references.pmid: 15303830
references.citation: Nature. 1968 Jul 13;219(5150):131-9
references.pmid: 5659637
references.citation: Chem Biol. 1999 Jan;6(1):R3-7
references.pmid: 9889153
references.citation: Structure. 2003 Nov;11(11):1453-9
references.pmid: 14604535
references.citation: Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915-9
references.pmid: 1438297
references.citation: Curr Opin Struct Biol. 2007 Feb;17(1):3-14
references.pmid: 17250999
references.citation: EMBO J. 1990 Aug;9(8):2351-9
references.pmid: 2196171
references.citation: Angew Chem Int Ed Engl. 2002 Aug 16;41(16):2879-90
references.pmid: 12203413
references.citation: J Mol Biol. 1997 Apr 25;268(1):170-84
references.pmid: 9149150
references.citation: Nat Rev Mol Cell Biol. 2005 Mar;6(3):197-208
references.pmid: 15738986
references.citation: Proteins. 2003 Nov 15;53(3):758-67
references.pmid: 14579366
references.citation: Science. 2001 Jul 20;293(5529):487-9
references.pmid: 11463915
references.citation: J Mol Biol. 2004 Mar 26;337(3):635-45
references.pmid: 15019783
references.citation: Genes Dev. 2005 Oct 15;19(20):2488-500
references.pmid: 16230536
references.citation: Genetika. 2002 Aug;38(8):1078-89
references.pmid: 12244692
references.citation: J Biol Chem. 2005 Sep 2;280(35):31276-82
references.pmid: 15905169
references.citation: Biomol NMR Assign. 2008 Jun;2(1):29-31
references.pmid: 19636917
references.citation: Biol Chem. 2003 Sep;384(9):1265-72
references.pmid: 14515987
references.citation: J Struct Biol. 2001 May-Jun;134(2-3):167-85
references.pmid: 11551177
references.citation: Science. 2000 Mar 24;287(5461):2204-15
references.pmid: 10731134
references.citation: Bioinformatics. 2008 Feb 1;24(3):426-7
references.pmid: 18174182
references.citation: Bioinformatics. 2008 Mar 15;24(6):872-3
references.pmid: 18227113
references.citation: J Mol Biol. 1999 Oct 22;293(2):321-31
references.pmid: 10550212
references.citation: Methods Enzymol. 2005;394:42-78
references.pmid: 15808217
references.citation: J Mol Biol. 1990 Jun 20;213(4):859-83
references.pmid: 2359125
references.citation: J Mol Biol. 1970 Mar;48(3):443-53
references.pmid: 5420325
references.citation: FEBS Lett. 2005 Jun 13;579(15):3346-54
references.pmid: 15943980
references.citation: Proteins. 2003;53 Suppl 6:573-8
references.pmid: 14579348
references.citation: J Struct Biol. 2005 Nov;152(2):113-7
references.pmid: 16242963
references.citation: Drug Discov Today. 2005 Apr 1;10(7):471-83
references.pmid: 15809193
references.citation: J Mol Biol. 2002 Oct 25;323(3):573-84
references.pmid: 12381310
references.citation: Curr Opin Struct Biol. 2002 Feb;12(1):54-60
references.pmid: 11839490
references.citation: Nature. 2007 Aug 16;448(7155):775-9
references.pmid: 17603473
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D668-72
references.pmid: 16381955
references.citation: Proteins. 2001 Jan 1;42(1):38-48
references.pmid: 11093259
references.citation: Bioinformatics. 2005 Aug 15;21(16):3433-4
references.pmid: 15955779
references.citation: J Chem Inf Comput Sci. 2003 Mar-Apr;43(2):391-405
references.pmid: 12653501
references.citation: J Biomol NMR. 1995 Jan;5(1):67-81
references.pmid: 7881273
references.citation: Glycoconj J. 2006 May;23(3-4):221-32
references.pmid: 16691505
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3701-8
references.pmid: 12824398
references.citation: Drug News Perspect. 2003 Mar;16(2):93-102
references.pmid: 12792670
references.citation: EMBO J. 2003 Jun 2;22(11):2583-92
references.pmid: 12773375
references.citation: Oncogene. 2006 Jul 6;25(29):4043-55
references.pmid: 16491116
references.citation: Nucleic Acids Res. 2007;35(4):1257-69
references.pmid: 17267410