title: A decade and a half of protein intrinsic disorder: biology still waits for physics.
abstract: The abundant existence of proteins and regions that possess specific functions without being uniquely folded into unique 3D structures has become accepted by a significant number of protein scientists. Sequences of these intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are characterized by a number of specific features, such as low overall hydrophobicity and high net charge which makes these proteins predictable. IDPs/IDPRs possess large hydrodynamic volumes, low contents of ordered secondary structure, and are characterized by high structural heterogeneity. They are very flexible, but some may undergo disorder to order transitions in the presence of natural ligands. The degree of these structural rearrangements varies over a very wide range. IDPs/IDPRs are tightly controlled under the normal conditions and have numerous specific functions that complement functions of ordered proteins and domains. When lacking proper control, they have multiple roles in pathogenesis of various human diseases. Gaining structural and functional information about these proteins is a challenge, since they do not typically "freeze" while their "pictures are taken." However, despite or perhaps because of the experimental challenges, these fuzzy objects with fuzzy structures and fuzzy functions are among the most interesting targets for modern protein research. This review briefly summarizes some of the recent advances in this exciting field and considers some of the basic lessons learned from the analysis of physics, chemistry, and biology of IDPs.
authors.affiliation: Department of Molecular Medicine, USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida 33612, USA. vuversky@health.usf.edu
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D011506:Proteins
references.citation: J Mol Biol. 2003 Mar 21;327(2):347-57
references.pmid: 12628242
references.citation: J Proteome Res. 2008 Jun;7(6):2234-45
references.pmid: 18465893
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17772-7
references.pmid: 19008353
references.citation: Comput Biol Chem. 2006 Aug;30(4):241-8
references.pmid: 16798096
references.citation: J R Soc Interface. 2008 Aug 6;5(25):953-6
references.pmid: 18426772
references.citation: Pac Symp Biocomput. 2001;:89-100
references.pmid: 11262981
references.citation: Biochemistry. 2000 Nov 7;39(44):13602-13
references.pmid: 11063598
references.citation: BMC Genomics. 2008;9 Suppl 1:S1
references.pmid: 18366598
references.citation: Gene. 2005 Jan 3;344:1-20
references.pmid: 15656968
references.citation: PLoS One. 2012;7(10):e47661
references.pmid: 23118886
references.citation: Membr Biochem. 1978;2(1):1-16
references.pmid: 45776
references.citation: Biochem Biophys Res Commun. 2009 Nov 13;389(2):388-93
references.pmid: 19733547
references.citation: Curr Opin Neurobiol. 1999 Oct;9(5):566-70
references.pmid: 10508741
references.citation: Intrinsically Disord Proteins. 2013 Apr 1;1(1):e24157
references.pmid: 28516007
references.citation: Curr Opin Struct Biol. 2005 Feb;15(1):35-41
references.pmid: 15718131
references.citation: Annu Rev Biophys. 2008;37:215-46
references.pmid: 18573080
references.citation: Cell Cycle. 2004 Apr;3(4):460-1
references.pmid: 14976429
references.citation: Curr Opin Chem Biol. 2010 Oct;14(5):671-5
references.pmid: 20832351
references.citation: Proc Natl Acad Sci U S A. 1990 Jan;87(2):638-42
references.pmid: 2300551
references.citation: Sci Am. 2000 Feb;282(2):90-5
references.pmid: 10710791
references.citation: Genome Biol. 2011 Jul 19;12(7):R65
references.pmid: 21771306
references.citation: Nature. 1998 Jun 4;393(6684):440-2
references.pmid: 9623998
references.citation: J Biomol Struct Dyn. 2007 Feb;24(4):325-42
references.pmid: 17206849
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12860-4
references.pmid: 15322276
references.citation: Proc Natl Acad Sci U S A. 2010 May 4;107(18):8183-8
references.pmid: 20404210
references.citation: Biochemistry. 1995 May 16;34(19):6278-87
references.pmid: 7756254
references.citation: Curr Opin Chem Biol. 2005 Jun;9(3):317-24
references.pmid: 15939335
references.citation: Chem Rev. 2006 Aug;106(8):3055-79
references.pmid: 16895318
references.citation: EMBO J. 1985 Jun;4(6):1593-7
references.pmid: 2992935
references.citation: PLoS Comput Biol. 2006 Aug 4;2(8):e100
references.pmid: 16884331
references.citation: Cell. 2007 Jan 26;128(2):269-80
references.pmid: 17254966
references.citation: Cell Mol Life Sci. 1999 Jun;55(6-7):977-91
references.pmid: 10412375
references.citation: FEBS Lett. 2006 Apr 3;580(8):2041-5
references.pmid: 16542654
references.citation: PLoS Comput Biol. 2008 Dec;4(12):e1000243
references.pmid: 19096501
references.citation: J Biol Chem. 2000 Sep 22;275(38):29426-32
references.pmid: 10884388
references.citation: EMBO J. 1997 Mar 3;16(5):968-77
references.pmid: 9118958
references.citation: Science. 1998 Feb 6;279(5352):851-3
references.pmid: 9452382
references.citation: J Am Chem Soc. 2009 Jun 3;131(21):7390-401
references.pmid: 19432426
references.citation: BMC Genomics. 2009 Jul 07;10 Suppl 1:S7
references.pmid: 19594884
references.citation: J Proteome Res. 2006 Apr;5(4):879-87
references.pmid: 16602695
references.citation: Hum Mol Genet. 2000 Apr 12;9(6):909-16
references.pmid: 10767314
references.citation: Genome Biol. 2008 Apr 09;9(4):R70
references.pmid: 18397532
references.citation: J Comput Chem. 2009 Apr 15;30(5):673-99
references.pmid: 18506808
references.citation: Mol Biol Evol. 2007 Apr;24(4):1005-11
references.pmid: 17264066
references.citation: Mol Biol Evol. 2011 Sep;28(9):2513-20
references.pmid: 21398349
references.citation: Nature. 2010 May 13;465(7295):219-22
references.pmid: 20463738
references.citation: Biochim Biophys Acta. 2012 Feb;1822(2):261-85
references.pmid: 22024360
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):113-8
references.pmid: 12518060
references.citation: F1000 Biol Rep. 2013;5:1
references.pmid: 23361308
references.citation: Science. 1996 Nov 8;274(5289):948-53
references.pmid: 8875929
references.citation: EMBO J. 1986 Nov;5(11):3021-7
references.pmid: 16453726
references.citation: J Am Chem Soc. 2011 Jun 22;133(24):9395-404
references.pmid: 21627157
references.citation: Nat Rev Drug Discov. 2004 Apr;3(4):301-17
references.pmid: 15060526
references.citation: J Mol Biol. 2008 Oct 17;382(4):971-7
references.pmid: 18680748
references.citation: Proteins. 2006 Oct 1;65(1):1-14
references.pmid: 16856179
references.citation: Curr Pharm Des. 2013;19(23):4191-213
references.pmid: 23170892
references.citation: Neuropharmacology. 2003 Jul;45(1):14-44
references.pmid: 12814657
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9205-10
references.pmid: 15197260
references.citation: J Proteome Res. 2007 May;6(5):1899-916
references.pmid: 17391015
references.citation: Nat Rev Mol Cell Biol. 2005 Mar;6(3):197-208
references.pmid: 15738986
references.citation: J Gen Physiol. 2010 Oct;136(4):483-94
references.pmid: 20876362
references.citation: Annu Rev Biochem. 1968;37:359-410
references.pmid: 4877056
references.citation: Biochim Biophys Acta. 2004 May 6;1698(2):131-53
references.pmid: 15134647
references.citation: Science. 1994 Feb 11;263(5148):777-84
references.pmid: 8303294
references.citation: Biophys J. 2007 Mar 1;92(5):1439-56
references.pmid: 17158572
references.citation: Biophys Chem. 2000 Aug 30;86(2-3):155-64
references.pmid: 11026680
references.citation: Protein J. 2009 Oct;28(7-8):305-25
references.pmid: 19768526
references.citation: Mol Cell Proteomics. 2010 Oct;9(10):2205-24
references.pmid: 20368288
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14609-14
references.pmid: 20639465
references.citation: J Mol Biol. 1978 Jan 5;118(1):99-112
references.pmid: 625059
references.citation: Biochemistry. 2002 Jul 2;41(26):8221-8
references.pmid: 12081470
references.citation: Science. 1989 Aug 4;245(4917):510-3
references.pmid: 2667138
references.citation: J Biomol Struct Dyn. 2012;30(2):137-49
references.pmid: 22702725
references.citation: Chem Rev. 2006 May;106(5):1737-56
references.pmid: 16683752
references.citation: Science. 2004 Feb 6;303(5659):844-8
references.pmid: 14704432
references.citation: Mol Biosyst. 2012 Jul 6;8(7):1886-901
references.pmid: 22543956
references.citation: N Engl J Med. 2001 May 17;344(20):1516-26
references.pmid: 11357156
references.citation: Biochemistry. 2007 Nov 27;46(47):13468-77
references.pmid: 17973494
references.citation: Protein Sci. 1996 Sep;5(9):1844-51
references.pmid: 8880908
references.citation: J Proteome Res. 2007 May;6(5):1917-32
references.pmid: 17391016
references.citation: Curr Protein Pept Sci. 2012 Feb;13(1):86-103
references.pmid: 22044151
references.citation: Biochemistry. 2006 Jul 25;45(29):8918-30
references.pmid: 16846235
references.citation: Trends Biotechnol. 2006 Oct;24(10):435-42
references.pmid: 16876893
references.citation: Adv Exp Med Biol. 2012;725:1-14
references.pmid: 22399315
references.citation: Protein Eng. 2000 Mar;13(3):149-52
references.pmid: 10775656
references.citation: Phys Biol. 2011 Jun;8(3):035002
references.pmid: 21572170
references.citation: J Am Chem Soc. 2008 Jul 23;130(29):9536-42
references.pmid: 18576630
references.citation: Biophys J. 2007 Sep 15;93(6):1923-37
references.pmid: 17526581
references.citation: J Mol Biol. 2004 Mar 26;337(3):635-45
references.pmid: 15019783
references.citation: EMBO J. 2006 Apr 19;25(8):1646-58
references.pmid: 16601693
references.citation: Biophys J. 1994 Oct;67(4):1691-705
references.pmid: 7819501
references.citation: Proteins. 2003 Dec 1;53(4):855-62
references.pmid: 14635127
references.citation: Cell Mol Life Sci. 2003 Jul;60(7):1427-39
references.pmid: 12943229
references.citation: Curr Opin Struct Biol. 1998 Feb;8(1):80-5
references.pmid: 9519299
references.citation: Genes Dev. 2001 Apr 15;15(8):925-32
references.pmid: 11316786
references.citation: J Mol Biol. 2002 Oct 18;323(2):327-44
references.pmid: 12381324
references.citation: J Proteome Res. 2006 Apr;5(4):888-98
references.pmid: 16602696
references.citation: Biochimie. 2007 Mar;89(3):419-21
references.pmid: 17174464
references.citation: Biochim Biophys Acta. 2013 Apr;1834(4):725-38
references.pmid: 23352836
references.citation: Mol Cancer Res. 2004 Jan;2(1):20-8
references.pmid: 14757842
references.citation: Nature. 1997 Apr 17;386(6626):657, 659
references.pmid: 9109481
references.citation: Biochim Biophys Acta. 1997 Sep 26;1342(1):73-82
references.pmid: 9366272
references.citation: Mol Biosyst. 2012 Jan;8(1):134-50
references.pmid: 21761058
references.citation: BMC Genomics. 2008;9 Suppl 1:S7
references.pmid: 18366620
references.citation: Nat Rev Neurosci. 2000 Nov;1(2):109-15
references.pmid: 11252773
references.citation: Eur J Biochem. 2002 Jan;269(1):2-12
references.pmid: 11784292
references.citation: Proteins. 2002 Jan 1;46(1):1-7
references.pmid: 11746698
references.citation: Mol Biosyst. 2012 Jan;8(1):220-8
references.pmid: 21922108
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):479-84
references.pmid: 17202261
references.citation: Biophys J. 1990 Apr;57(4):911-21
references.pmid: 2188687
references.citation: Curr Opin Struct Biol. 1996 Feb;6(1):3-10
references.pmid: 8696970
references.citation: J Mol Evol. 2007 Sep;65(3):277-88
references.pmid: 17721672
references.citation: Trends Biochem Sci. 1999 Sep;24(9):329-32
references.pmid: 10470028
references.citation: Genome Biol. 2006;7(6):R45
references.pmid: 16780599
references.citation: Curr Opin Struct Biol. 2008 Dec;18(6):756-64
references.pmid: 18952168
references.citation: J Mol Evol. 1998 Jan;46(1):1-17
references.pmid: 9419221
references.citation: Genome Inform Ser Workshop Genome Inform. 2000;11:172-84
references.pmid: 11700598
references.citation: J Mol Biol. 2006 Jun 16;359(4):1137-49
references.pmid: 16697407
references.citation: Protein Pept Lett. 2010 Aug;17(8):932-51
references.pmid: 20450483
references.citation: Chem Biol. 2000 Apr;7(4):R85-94
references.pmid: 10779412
references.citation: Cell Death Differ. 2013 Sep;20(9):1257-67
references.pmid: 23764774
references.citation: Mol Biosyst. 2009 Dec;5(12):1688-1702
references.pmid: 19585006
references.citation: Chemphyschem. 2009 Jul 13;10(9-10):1415-9
references.pmid: 19462392
references.citation: Protein Eng. 1999 Sep;12(9):713-20
references.pmid: 10506280
references.citation: Cell Mol Life Sci. 2014 Apr;71(8):1477-504
references.pmid: 23942625
references.citation: Nature. 1978 Nov 23;276(5686):362-8
references.pmid: 19711551
references.citation: J Mol Biol. 1999 Oct 22;293(2):321-31
references.pmid: 10550212
references.citation: Biochemistry. 2008 Dec 9;47(49):12942-4
references.pmid: 19012413
references.citation: Brain Res Bull. 2001 Oct-Nov 1;56(3-4):161-3
references.pmid: 11719245
references.citation: Proc Natl Acad Sci U S A. 1975 May;72(5):1909-12
references.pmid: 1057181
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12583-8
references.pmid: 12239345
references.citation: Nat Struct Biol. 1997 Oct;4(10):805-9
references.pmid: 9334745
references.citation: J Mol Biol. 1968 Dec;38(3):367-79
references.pmid: 4887876
references.citation: J Mol Recognit. 2010 Mar-Apr;23(2):105-16
references.pmid: 19585546
references.citation: Biochem Biophys Res Commun. 1984 Aug 16;122(3):1131-5
references.pmid: 6236805
references.citation: Mol Biochem Parasitol. 2006 Dec;150(2):256-67
references.pmid: 17010454
references.citation: Bioinformatics. 2006 Jul 1;22(13):1546-50
references.pmid: 16601002
references.citation: Structure. 2010 Mar 14;18(4):494-506
references.pmid: 20399186
references.citation: Biochemistry. 2006 Jun 6;45(22):6873-88
references.pmid: 16734424
references.citation: Science. 1991 Feb 8;251(4994):675-8
references.pmid: 1899488
references.citation: FEBS Lett. 2005 Jun 13;579(15):3346-54
references.pmid: 15943980
references.citation: J Proteome Res. 2006 Nov;5(11):2985-95
references.pmid: 17081050
references.citation: Int J Biochem Cell Biol. 2011 Aug;43(8):1090-103
references.pmid: 21501695
references.citation: Science. 2008 Nov 28;322(5906):1365-8
references.pmid: 19039133
references.citation: Proteins. 2006 May 1;63(2):297-311
references.pmid: 16299774
references.citation: FEBS J. 2009 Jul;276(14):3744-56
references.pmid: 19523119
references.citation: J Mol Biol. 2002 Oct 25;323(3):573-84
references.pmid: 12381310
references.citation: Curr Opin Pharmacol. 2010 Dec;10(6):706-8
references.pmid: 20951643
references.citation: Biochemistry. 2008 Dec 23;47(51):13489-96
references.pmid: 19053245
references.citation: Protein Sci. 2013 Mar;22(3):258-73
references.pmid: 23233352
references.citation: PLoS Comput Biol. 2010 Jun 17;6(6):e1000817
references.pmid: 20585543
references.citation: Methods Mol Biol. 2008;426:103-15
references.pmid: 18542859
references.citation: J Biol Chem. 2001 Apr 6;276(14):10737-44
references.pmid: 11152691
references.citation: BMC Genomics. 2008 Sep 16;9 Suppl 2:S1
references.pmid: 18831774
references.citation: Curr Opin Struct Biol. 2002 Feb;12(1):54-60
references.pmid: 11839490
references.citation: Curr Opin Struct Biol. 2011 Jun;21(3):441-6
references.pmid: 21482101
references.citation: Nat Biotechnol. 2001 Sep;19(9):805-6
references.pmid: 11533628
references.citation: Proteins. 2001 Jan 1;42(1):38-48
references.pmid: 11093259
references.citation: Annu Rev Biophys Biophys Chem. 1991;20:447-90
references.pmid: 1867723
references.citation: Cell Res. 2009 Aug;19(8):929-49
references.pmid: 19597536
references.citation: Bioinformatics. 2005 Aug 15;21(16):3433-4
references.pmid: 15955779
references.citation: J Mol Biol. 1989 Sep 5;209(1):127-33
references.pmid: 2810365
references.citation: J Proteome Res. 2006 Aug;5(8):1996-2000
references.pmid: 16889422
references.citation: J Biol Chem. 1994 Sep 30;269(39):24290-7
references.pmid: 7929085
references.citation: Cell Cycle. 2004 Apr;3(4):419-21
references.pmid: 15004525
references.citation: Neurology. 1985 Jul;35(7):957-61
references.pmid: 3159974
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9650-5
references.pmid: 17522259
references.citation: Biochim Biophys Acta. 2010 Jun;1804(6):1231-64
references.pmid: 20117254
references.citation: Nucleic Acids Res. 2004 Feb 11;32(3):1037-49
references.pmid: 14960716
references.citation: Protein Eng. 1994 Nov;7(11):1373-7
references.pmid: 7700869
references.citation: Science. 1999 Oct 15;286(5439):509-12
references.pmid: 10521342
references.citation: EMBO J. 1985 Nov;4(11):2757-63
references.pmid: 4065091
references.citation: Mol Biosyst. 2008 Apr;4(4):328-40
references.pmid: 18354786
references.citation: Trends Biochem Sci. 2005 Sep;30(9):484-9
references.pmid: 16054818
references.citation: Curr Opin Struct Biol. 2001 Jun;11(3):309-14
references.pmid: 11406379
references.citation: Science. 1988 Nov 4;242(4879):762-5
references.pmid: 2460920
references.citation: J Mol Biol. 2008 Dec 5;384(1):279-97
references.pmid: 18824003
references.citation: Br J Cancer. 2004 Oct 18;91(8):1415-9
references.pmid: 15452548
references.citation: Phys Rev Lett. 2005 Sep 9;95(11):118102
references.pmid: 16197051
references.citation: Curr Opin Struct Biol. 2000 Feb;10(1):60-8
references.pmid: 10679462
references.citation: Mol Cell Biochem. 1975 Jul 31;8(1):5-20
references.pmid: 170505
references.citation: Biochemistry. 2004 Feb 24;43(7):2049-61
references.pmid: 14967045
references.citation: J Mol Evol. 1998 Jan;46(1):18-36
references.pmid: 9419222
references.citation: Protein Pept Lett. 2008;15(9):956-63
references.pmid: 18991772
references.citation: Biochemistry. 1987 Jan 27;26(2):418-23
references.pmid: 3828315
references.citation: J Proteome Res. 2009 Jan;8(1):211-26
references.pmid: 19067583
references.citation: Protein Pept Lett. 2003 Jun;10(3):239-45
references.pmid: 12871143
references.citation: Curr Opin Struct Biol. 2009 Feb;19(1):31-8
references.pmid: 19157855
references.citation: Nat Chem Biol. 2008 Dec;4(12):728-37
references.pmid: 19008886
references.citation: Prog Biophys Mol Biol. 2008 Sep;98(1):85-106
references.pmid: 18619997
references.citation: Genome Biol. 2002;3(1):REVIEWS3002
references.pmid: 11806835
references.citation: Protein Sci. 2002 Dec;11(12):2804-13
references.pmid: 12441379
references.citation: J Mol Biol. 1977 May 25;112(3):535-42
references.pmid: 875032
references.citation: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8390-5
references.pmid: 16717195
references.citation: J Proteome Res. 2007 May;6(5):1882-98
references.pmid: 17391014
references.citation: Nature. 1973 Nov 2;246(5427):22-6
references.pmid: 4585842
references.citation: J Proteome Res. 2002 Mar-Apr;1(2):149-59
references.pmid: 12643535
references.citation: PLoS One. 2010 Aug 11;5(8):e12069
references.pmid: 20711457
references.citation: Expert Opin Drug Discov. 2012 Jun;7(6):475-88
references.pmid: 22559227
references.citation: Nat Biotechnol. 2004 Sep;22(9):1081-4
references.pmid: 15340471
references.citation: Science. 1959 Jul 31;130(3370):245-51
references.pmid: 13668555
references.citation: Pac Symp Biocomput. 1998;:473-84
references.pmid: 9697205
references.citation: Science. 1953 May 15;117(3046):528-9
references.pmid: 13056598
references.citation: Ann Med. 2003;35(1):28-35
references.pmid: 12693610
references.citation: Mol Biosyst. 2012 Oct 30;8(12):3262-73
references.pmid: 23076520
references.citation: Eur J Biochem. 1978 Sep 1;89(2):475-82
references.pmid: 710406
references.citation: Biochim Biophys Acta. 2011 May;1814(5):693-712
references.pmid: 21440685
references.citation: Genome Biol. 2008;9(7):R107
references.pmid: 18606003
references.citation: Biochemistry. 1999 Nov 9;38(45):15009-16
references.pmid: 10555983
references.citation: J Biol Chem. 1998 Feb 6;273(6):3718-24
references.pmid: 9452503
references.citation: Trends Biochem Sci. 1993 May;18(5):181-6
references.pmid: 8328018
references.citation: J Biomol Struct Dyn. 2003 Oct;21(2):211-34
references.pmid: 12956606
references.citation: Trends Biochem Sci. 1999 Jan;24(1):8-11
references.pmid: 10087914
references.citation: Nat Struct Biol. 1998 Jul;5(7):568-70
references.pmid: 9665170
references.citation: Genome Inform Ser Workshop Genome Inform. 1999;10:41-50
references.pmid: 11072341
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11282-6
references.pmid: 8248242
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11504-9
references.pmid: 8876165
references.citation: Bioessays. 2009 Mar;31(3):328-35
references.pmid: 19260013
references.citation: Biophys J. 2013 Jan 22;104(2):488-95
references.pmid: 23442871
references.citation: Adv Protein Chem. 1995;47:83-229
references.pmid: 8561052
references.citation: J Am Chem Soc. 2008 Jun 11;130(23):7380-92
references.pmid: 18481860
references.citation: J Mol Recognit. 2005 Sep-Oct;18(5):343-84
references.pmid: 16094605
references.citation: Adv Protein Chem. 2002;62:25-49
references.pmid: 12418100
references.citation: Br J Cancer. 2001 Dec 14;85(12):1813-23
references.pmid: 11747320
references.citation: Int J Mol Sci. 2009 Apr 08;10(4):1567-1589
references.pmid: 19468326
references.citation: Biochemistry. 2005 Sep 20;44(37):12454-70
references.pmid: 16156658
references.citation: J Biomed Biotechnol. 2010;2010:568068
references.pmid: 20011072
references.citation: Gene. 2000 Dec 30;261(1):139-51
references.pmid: 11164045
references.citation: Biochim Biophys Acta. 2013 May;1834(5):932-51
references.pmid: 23269364
references.citation: Pac Symp Biocomput. 1999;:578-89
references.pmid: 10380229
references.citation: Science. 2008 Nov 28;322(5906):1340-1
references.pmid: 19039128
references.citation: PLoS Biol. 2009 Dec;7(12):e1000257
references.pmid: 20016684
references.citation: BMC Syst Biol. 2010 May 28;4 Suppl 1:S1
references.pmid: 20522251
references.citation: FEBS Lett. 1999 Oct 8;459(2):267-71
references.pmid: 10518033
references.citation: Proc Natl Acad Sci U S A. 1966 Dec;56(6):1828-35
references.pmid: 16591427
references.citation: Chembiochem. 2013 Feb 11;14(3):285-92
references.pmid: 23362046
references.citation: FASEB J. 2004 Aug;18(11):1169-75
references.pmid: 15284216
references.citation: FEBS J. 2005 Oct;272(20):5129-48
references.pmid: 16218947
references.citation: Proteins. 2008 Mar;70(4):1357-66
references.pmid: 17879262
references.citation: Curr Opin Struct Biol. 1998 Feb;8(1):101-6
references.pmid: 9519302
references.citation: Proteins. 2000 Feb 1;38(2):121-2
references.pmid: 10656259
references.citation: Biochemistry. 2006 Dec 26;45(51):15731-9
references.pmid: 17176095
references.citation: Science. 1991 Jul 5;253(5015):49-53
references.pmid: 1905840
references.citation: BMC Struct Biol. 2011 Dec 22;11:50
references.pmid: 22192175
references.citation: Prog Nucleic Acid Res Mol Biol. 2002;72:223-68
references.pmid: 12206453
references.citation: Biochemistry. 1996 Oct 29;35(43):13709-15
references.pmid: 8901511
references.citation: J Mol Biol. 2010 Mar 12;396(5):1295-309
references.pmid: 20026071
references.citation: Genome Inform Ser Workshop Genome Inform. 2000;11:161-71
references.pmid: 11700597
references.citation: F1000 Biol Rep. 2013;5:2
references.pmid: 23361309
references.citation: Proteins. 2000 Nov 15;41(3):415-27
references.pmid: 11025552
references.citation: Chem Soc Rev. 2011 Mar;40(3):1623-34
references.pmid: 21049125
references.citation: J Biol Chem. 2004 Feb 27;279(9):7982-7
references.pmid: 14625282
references.citation: Biochem Soc Trans. 2003 Jun;31(Pt 3):677-80
references.pmid: 12773181
references.citation: Nat Chem Biol. 2008 Apr;4(4):229-30
references.pmid: 18347590
references.citation: Trends Biochem Sci. 1997 May;22(5):147-9
references.pmid: 9175467
references.citation: J Biol Chem. 2005 Feb 11;280(6):4684-95
references.pmid: 15542602
references.citation: Nat Struct Biol. 1999 Nov;6(11):1033-8
references.pmid: 10542095
references.citation: Adv Biophys. 1984;18:165-90
references.pmid: 6100468
references.citation: Trends Biochem Sci. 2008 Jan;33(1):2-8
references.pmid: 18054235
references.citation: Proc Natl Acad Sci U S A. 2008 May 20;105(20):7177-81
references.pmid: 18477697
references.citation: J Mol Biol. 2007 May 4;368(3):902-13
references.pmid: 17368479
references.citation: J Biomol Struct Dyn. 2012;29(5):843-61
references.pmid: 22292947
references.citation: Genome Inform Ser Workshop Genome Inform. 1998;9:201-213
references.pmid: 11072336
references.citation: Proteins. 2007 Aug 15;68(3):602-5
references.pmid: 17510967
references.citation: Extremophiles. 2000 Apr;4(2):91-8
references.pmid: 10805563
references.citation: Trends Biochem Sci. 2002 Oct;27(10):527-33
references.pmid: 12368089
references.citation: Eur Biophys J. 2007 Nov;36(8):1059-69
references.pmid: 17565494
references.citation: J Mol Biol. 1998 Jul 24;280(4):731-48
references.pmid: 9677300
references.citation: Biochemistry. 2000 Mar 14;39(10):2708-13
references.pmid: 10704222
references.citation: Curr Opin Pharmacol. 2010 Dec;10(6):782-8
references.pmid: 20889377
references.citation: Biochemistry. 1998 Sep 15;37(37):12689-99
references.pmid: 9737845
references.citation: Biochemistry. 2005 Feb 15;44(6):1989-2000
references.pmid: 15697224
references.citation: Nat Struct Mol Biol. 2007 Dec;14(12):1202-6
references.pmid: 17994104
references.citation: FEBS Lett. 2008 Apr 9;582(8):1271-5
references.pmid: 18284921
references.citation: J Biol Chem. 1974 Dec 25;249(24):8019-29
references.pmid: 4609976
references.citation: J Mol Evol. 2002 Jul;55(1):104-10
references.pmid: 12165847
references.citation: Pac Symp Biocomput. 1998;:437-48
references.pmid: 9697202
references.citation: Protein Eng Des Sel. 2005 Jun;18(6):279-84
references.pmid: 15928003
references.citation: Proteins. 2007 Mar 1;66(4):761-5
references.pmid: 17154416
references.citation: Curr Protein Pept Sci. 2007 Apr;8(2):135-49
references.pmid: 17430195
references.citation: J Proteome Res. 2008 Jun;7(6):2496-506
references.pmid: 18435556
references.citation: Annu Rev Biochem. 2006;75:519-41
references.pmid: 16756501
references.citation: Curr Opin Struct Biol. 2004 Dec;14(6):663-8
references.pmid: 15582389
references.citation: Curr Protein Pept Sci. 2007 Apr;8(2):161-71
references.pmid: 17430197
references.citation: Cancer Res. 2004 Apr 15;64(8):2766-73
references.pmid: 15087392
references.citation: Proteins. 1999 Jul 1;36(1):135-43
references.pmid: 10373012
references.citation: J Biol Chem. 1999 Dec 10;274(50):35521-5
references.pmid: 10585425
references.citation: J Mol Graph Model. 2001;19(1):26-59
references.pmid: 11381529
references.citation: BMC Bioinformatics. 2007 Jun 19;8:211
references.pmid: 17578581
references.citation: Biochemistry. 2002 May 28;41(21):6573-82
references.pmid: 12022860
references.citation: Trends Biochem Sci. 1990 Sep;15(9):333-7
references.pmid: 2238041
references.citation: Cell Mol Life Sci. 2003 Sep;60(9):1852-71
references.pmid: 14523548
references.citation: Clin Cancer Res. 2010 Aug 15;16(16):4077-83
references.pmid: 20547696
references.citation: Protein Sci. 2002 Apr;11(4):739-56
references.pmid: 11910019