title: Intrinsically disordered proteins in a physics-based world.
abstract: Intrinsically disordered proteins (IDPs) are a newly recognized class of functional proteins that rely on a lack of stable structure for function. They are highly prevalent in biology, play fundamental roles, and are extensively involved in human diseases. For signaling and regulation, IDPs often fold into stable structures upon binding to specific targets. The mechanisms of these coupled binding and folding processes are of significant importance because they underlie the organization of regulatory networks that dictate various aspects of cellular decision-making. This review first discusses the challenge in detailed experimental characterization of these heterogeneous and dynamics proteins and the unique and exciting opportunity for physics-based modeling to make crucial contributions, and then summarizes key lessons from recent de novo simulations of the structure and interactions of several regulatory IDPs.
authors: Department of Biochemistry, Kansas State University, Manhattan, KS 66506, USA.
authors: Timothy H
authors: TH
authors: Click
authors: Debabani
authors: D
authors: Ganguly
authors: Jianhan
authors: J
authors: Chen
references: Protein Sci. 2006 Dec;15(12):2795-804
references: 17088319
references: J Mol Biol. 2010 Feb 26;396(3):674-84
references: 19958775
references: PLoS One. 2009 Aug 05;4(8):e6516
references: 19654879
references: FEBS Lett. 1998 Jul 3;430(3):317-22
references: 9688563
references: J Am Chem Soc. 2010 Feb 10;132(5):1526-8
references: 20070076
references: J Mol Biol. 2005 Nov 11;353(5):1118-28
references: 16214166
references: Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10890-5
references: 20534497
references: Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17772-7
references: 19008353
references: J Phys Chem B. 2010 Jul 8;114(26):8790-8
references: 20536262
references: BMC Genomics. 2008;9 Suppl 1:S1
references: 18366598
references: J Am Chem Soc. 2010 Feb 3;132(4):1270-2
references: 20063887
references: Oncogene. 2007 Apr 2;26(15):2226-42
references: 17401432
references: Science. 2000 Dec 8;290(5498):1903-4
references: 17742054
references: Curr Opin Struct Biol. 2005 Feb;15(1):35-41
references: 15718131
references: Annu Rev Biophys. 2008;37:215-46
references: 18573080
references: Chem Rev. 2006 May;106(5):1898-916
references: 16683760
references: J Mol Recognit. 2007 Nov-Dec;20(6):495-501
references: 17902095
references: Proc Natl Acad Sci U S A. 2007 May 15;104(20):8311-5
references: 17494761
references: Phys Chem Chem Phys. 2008 Jan 28;10(4):471-81
references: 18183310
references: Curr Opin Struct Biol. 2007 Feb;17(1):15-20
references: 17239581
references: Proc Natl Acad Sci U S A. 2010 May 4;107(18):8183-8
references: 20404210
references: J Comput Chem. 2003 Nov 15;24(14):1691-702
references: 12964188
references: Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5762-7
references: 18391200
references: Proteins. 2006 May 1;63(2):391-7
references: 16288455
references: J Chem Theory Comput. 2008 Apr;4(4):626-36
references: 26620937
references: J Mol Biol. 2007 Sep 21;372(3):708-22
references: 17681539
references: Science. 2009 Apr 10;324(5924):198-203
references: 19359576
references: J Mol Biol. 2004 May 14;338(5):1015-26
references: 15111064
references: Nature. 2007 Jun 21;447(7147):1021-5
references: 17522630
references: J Biomol NMR. 1999 Mar;13(3):289-302
references: 10212987
references: Curr Opin Struct Biol. 2007 Feb;17(1):3-14
references: 17250999
references: J Comput Chem. 2009 Apr 15;30(5):673-99
references: 18506808
references: J Mol Biol. 1997 Apr 25;268(1):170-84
references: 9149150
references: Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6278-83
references: 18434548
references: Nat Rev Mol Cell Biol. 2005 Mar;6(3):197-208
references: 15738986
references: Methods. 2009 Oct;49(2):197-201
references: 19410002
references: J Am Chem Soc. 2007 Jan 31;129(4):820-7
references: 17243818
references: Biophys J. 2010 Aug 4;99(3):L26-8
references: 20682244
references: Science. 2001 Jul 20;293(5529):487-9
references: 11463915
references: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16880-5
references: 17942695
references: Drug Discov Today. 2003 Apr 15;8(8):347-55
references: 12681938
references: J Mol Biol. 2007 Sep 14;372(2):549-61
references: 17681540
references: Nature. 1993 Oct 28;365(6449):855-9
references: 8413673
references: J Chem Phys. 2009 Sep 28;131(12):124101
references: 19791846
references: J Am Chem Soc. 2010 Apr 7;132(13):4702-9
references: 20218718
references: J Chem Phys. 2007 Jan 7;126(1):014903
references: 17212515
references: Curr Top Med Chem. 2007;7(10):943-51
references: 17508925
references: Biophys J. 2010 May 19;98(10):2383-90
references: 20483348
references: J Am Chem Soc. 2007 Mar 14;129(10):2930-7
references: 17302414
references: Proteins. 2009;77 Suppl 9:210-6
references: 19774619
references: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15340-5
references: 17878309
references: Mol Cell Biol. 1996 Feb;16(2):694-703
references: 8552098
references: J Am Chem Soc. 2004 Mar 17;126(10):3291-9
references: 15012160
references: J Mol Biol. 2007 Apr 13;367(5):1494-510
references: 17320108
references: Curr Opin Struct Biol. 2008 Dec;18(6):756-64
references: 18952168
references: J Am Chem Soc. 2008 Jun 25;130(25):7804-5
references: 18512919
references: J Mol Biol. 1999 Oct 22;293(2):321-31
references: 10550212
references: Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8868-73
references: 10908673
references: J Chem Phys. 2008 Jan 14;128(2):024103
references: 18205439
references: Curr Opin Struct Biol. 2009 Feb;19(1):23-30
references: 19162471
references: Biophys J. 2008 Jul;95(1):L07-9
references: 18456823
references: Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18546-50
references: 17116871
references: J Comput Chem. 2004 Oct;25(13):1584-604
references: 15264253
references: Structure. 2010 Mar 14;18(4):494-506
references: 20399186
references: J Chem Phys. 2005 Oct 15;123(15):154105
references: 16252940
references: J Am Chem Soc. 2007 Mar 7;129(9):2444-5
references: 17288425
references: J Mol Biol. 2002 Oct 25;323(3):573-84
references: 12381310
references: Adv Protein Chem. 2003;66:27-85
references: 14631816
references: Annu Rev Phys Chem. 2007;58:57-83
references: 17034338
references: J Am Chem Soc. 2009 Apr 15;131(14):5214-23
references: 19278259
references: Proteins. 2007 Jan 1;66(1):53-60
references: 17063490
references: Protein Sci. 2009 Feb;18(2):337-47
references: 19165719
references: J Comput Chem. 2006 Oct;27(13):1477-85
references: 16823811
references: J Comput Chem. 2003 Jan 15;24(1):21-31
references: 12483672
references: J Am Chem Soc. 2006 Mar 22;128(11):3728-36
references: 16536547
references: Curr Opin Struct Biol. 2009 Feb;19(1):31-8
references: 19157855
references: Proteins. 2006 Jan 1;62(1):24-45
references: 16287116
references: Nat Struct Mol Biol. 2009 Jun;16(6):582-8
references: 19491935
references: Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2746-50
references: 20133683
references: Curr Opin Struct Biol. 2008 Feb;18(1):4-9
references: 18242977
references: J Chem Phys. 2004 Dec 1;121(21):10748-56
references: 15549960
references: J Mol Biol. 2009 Jul 17;390(3):467-77
references: 19447112
references: Chem Rev. 2004 Aug;104(8):3607-22
references: 15303830
references: Mol Cell. 1998 Sep;2(3):353-9
references: 9774973
references: Proteins. 2007 May 15;67(3):526-30
references: 17335006
references: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11504-9
references: 8876165
references: Proc Natl Acad Sci U S A. 1988 Apr;85(7):2029-30
references: 3353365
references: J Am Chem Soc. 2008 Jun 11;130(23):7380-92
references: 18481860
references: Curr Opin Struct Biol. 2004 Oct;14(5):570-6
references: 15465317
references: J Mol Recognit. 2005 Sep-Oct;18(5):343-84
references: 16094605
references: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5148-53
references: 12697905
references: J Comput Chem. 2008 Jul 30;29(10):1640-9
references: 18293296
references: Curr Opin Struct Biol. 2007 Apr;17(2):187-91
references: 17382533
references: J Am Chem Soc. 2008 Jun 25;130(25):8055-61
references: 18507376
references: Proteins. 2007 Jun 1;67(4):922-30
references: 17373704
references: Biophys Chem. 1999 Apr 5;78(1-2):1-20
references: 17030302
references: J Mol Biol. 2007 Sep 21;372(3):689-707
references: 17681534
references: Phys Rev Lett. 2007 Mar 23;98(12):128105
references: 17501161
references: J Chem Theory Comput. 2010;6(3):787-94
references: 23626502
references: Chemphyschem. 2008 May 16;9(7):954-66
references: 18348129
references: Curr Opin Struct Biol. 2008 Apr;18(2):140-8
references: 18304802
references: J Biol Chem. 2002 Nov 1;277(44):42241-8
references: 12196545
references: FEBS J. 2005 Oct;272(20):5129-48
references: 16218947
references: J Biomol NMR. 1994 Mar;4(2):171-80
references: 8019132
references: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17002-7
references: 16284250
references: Chem Rev. 2008 Apr;108(4):1225-44
references: 18355092
references: J Mol Biol. 1997 Apr 25;268(1):158-69
references: 9149149
references: Nature. 2002 Jan 31;415(6871):549-53
references: 11823864
references: Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13099-104
references: 16131545
references: J Am Chem Soc. 2008 Aug 27;130(34):11477-85
references: 18681437
references: Trends Biochem Sci. 2002 Oct;27(10):527-33
references: 12368089
references: J Am Chem Soc. 2009 Feb 18;131(6):2088-9
references: 19216110
references: Biochem Soc Trans. 2008 Dec;36(Pt 6):1404-8
references: 19021564
references: Biochemistry. 2002 Jan 22;41(3):752-9
references: 11790096
references: Curr Protein Pept Sci. 2007 Apr;8(2):135-49
references: 17430195
references: J Am Chem Soc. 2003 Feb 19;125(7):1722-30
references: 12580597
references: Adv Protein Chem. 1973;27:1-109
references: 4589664
references: Biochemistry. 2006 Aug 8;45(31):9363-73
references: 16878971
references: Cell. 1997 Dec 12;91(6):741-52
references: 9413984
references: J Mol Graph Model. 2001;19(1):26-59
references: 11381529
references: Proteins. 2010 Jun;78(8):1950-8
references: 20408171
references: J Am Chem Soc. 2001 Feb 21;123(7):1541-2
references: 11456746
references: Biochemistry. 2002 May 28;41(21):6573-82
references: 12022860
references: J Am Chem Soc. 2007 Mar 21;129(11):3056-7
references: 17311386
references: J Chem Theory Comput. 2006 Nov;2(6):1693
references: 26627040