Unmet challenges of structural genomics.
Structural genomics (SG) programs have developed during the last decade many novel methodologies for faster and more accurate structure determination. These new tools and approaches led to the determination of thousands of protein structures. The generation of enormous amounts of experimental data resulted in significant improvements in the understanding of many biological processes at molecular levels. However, the amount of data collected so far is so large that traditional analysis methods are limiting the rate of extraction of biological and biochemical information from 3D models. This situation has prompted us to review the challenges that remain unmet by SG, as well as the areas in which the potential impact of SG could exceed what has been achieved so far.
Chruszcz
Maksymilian
M
Department of Molecular Physiology and Biological Physics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
Domagalski
Marcin
M
Osinski
Tomasz
T
Wlodawer
Alexander
A
Minor
Wladek
W
D000818:Animals; D003460:Crystallization; D055808:Drug Discovery; D023281:Genomics / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D011506:Proteins
J Struct Funct Genomics. 2006 Jun;7(2):65-76
17146617
Proteins. 2005 May 15;59(3):633-43
15789406
Curr Opin Microbiol. 2009 Oct;12(5):547-52
19695948
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
20057044
Biochemistry. 2010 Apr 13;49(14):2987-98
20235548
J Med Chem. 2010 Feb 11;53(3):1402-6
20067275
Curr Opin Chem Biol. 2008 Feb;12(1):32-9
18282486
Infect Disord Drug Targets. 2009 Nov;9(5):493-506
19594426
Nat Biotechnol. 2009 Jan;27(1):51-7
19079241
Chem Biol. 2008 Dec 22;15(12):1296-306
19101474
Structure. 2008 Jan;16(1):14-6
18184577
Methods Mol Biol. 2010;607:127-47
20204854
PLoS Biol. 2009 Sep;7(9):e1000205
19787035
Annu Rev Biochem. 2009;78:541-68
19489729
Nat Rev Drug Discov. 2007 Jan;6(1):29-40
17159923
Bioinformatics. 2007 Dec 15;23(24):3403-5
17921170
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):426-36
20382996
Cryst Growth Des. 2009 Dec 18;10(2):580
20161694
Curr Opin Struct Biol. 2009 Oct;19(5):573-84
19765976
J Med Chem. 2010 Apr 8;53(7):2709-18
20232802
Nat Chem Biol. 2009 Jul;5(7):436-40
19536100
Drug Discov Today. 2009 Jul;14(13-14):676-83
19422931
Chem Pharm Bull (Tokyo). 2010 Jan;58(1):66-75
20045969
BMC Struct Biol. 2008 Oct 27;8:45
18954462
Structure. 2009 Jun 10;17(6):869-81
19523904
Science. 2009 Sep 18;325(5947):1544-9
19762644
Infect Disord Drug Targets. 2009 Nov;9(5):507-17
19860716
PLoS Comput Biol. 2009 Oct;5(10):e1000530
19855826
Brief Funct Genomic Proteomic. 2008 Jul;7(4):291-302
18599513
Acta Crystallogr D Biol Crystallogr. 2006 Oct;62(Pt 10):1184-95
17001095
Proteins. 2009;77 Suppl 9:1-4
19774620
PLoS One. 2009 Oct 20;4(10):e7394
19841676
PLoS Comput Biol. 2009 Dec;5(12):e1000605
20011109
J Inorg Biochem. 2008 Sep;102(9):1765-76
18614239
Curr Opin Struct Biol. 2008 Aug;18(4):499-506
18638552
Nat Biotechnol. 2007 Aug;25(8):849-51
17687356
Biochem Biophys Res Commun. 2010 Jan 1;391(1):1131-5
20005197
Cell Mol Life Sci. 2009 Nov;66(22):3625-39
19690801
J Biomol NMR. 2004 Nov;30(3):311-25
15754057
Drug Discov Today. 2006 Jan;11(1-2):28-34
16478688
Exp Cell Res. 2010 May 1;316(8):1332-8
20211166
Genome Biol. 2008;9(8):R121
18673581
Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):116-24
16369101
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
20383002
Methods Mol Biol. 2004;266:231-59
15148422
Nat Methods. 2008 Feb;5(2):135-46
18235434
Acta Crystallogr D Biol Crystallogr. 2003 Jun;59(Pt 6):1028-37
12777766
Methods Mol Biol. 2008;426:331-41
18542874
PLoS One. 2009;4(4):e5094
19352432
J Appl Crystallogr. 2009 Jun 1;42(Pt 3):376-384
22477769
Science. 2007 Jul 13;317(5835):195-6
17626865
J Synchrotron Radiat. 2009 May;16(Pt 3):413-21
19395808
Nat Methods. 2009 Aug;6(8):606-12
19620974
Acta Crystallogr D Biol Crystallogr. 2005 Aug;61(Pt 8):1165-71
16041083
Methods Mol Biol. 2008;426:299-318
18542872
Adv Protein Chem Struct Biol. 2009;77:23-40
20663480
Nucleic Acids Res. 2009 Jan;37(Database issue):D365-8
19010965
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W89-93
15980588
Methods Mol Biol. 2008;426:497-513
18542886
Structure. 2008 Nov 12;16(11):1668-77
19000819
Nat Chem Biol. 2007 Aug;3(8):486-91
17603539
FEBS J. 2008 Jan;275(1):1-21
18034855
Curr Opin Struct Biol. 2005 Oct;15(5):548-55
16154351
Curr Opin Microbiol. 2009 Jun;12(3):318-25
19481971
Acta Crystallogr D Biol Crystallogr. 2008 Nov;64(Pt 11):1116-22
19020349
Proteins. 2010 Jun;78(8):1939-49
20408170
Proteins. 2009;77 Suppl 9:10-7
19603487
Curr Opin Struct Biol. 2009 Aug;19(4):449-57
19477632
J Chem Inf Model. 2009 Nov;49(11):2512-27
19845314
Database (Oxford). 2009;2009:bap016
20157489
PLoS Comput Biol. 2010 Apr 01;6(4):e1000727
20369011
Infect Disord Drug Targets. 2009 Nov;9(5):459-74
19594422
Acta Crystallogr D Biol Crystallogr. 2009 Feb;65(Pt 2):176-85
19171973
Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19243-8
17159147
Drug Discov Today. 2009 Nov;14(21-22):1006-10
19815089
Proteins. 2007 Mar 1;66(4):778-95
17186527
Nat Methods. 2008 Oct;5(10):853-4
18825126
Nat Methods. 2007 Dec;4(12):1019-21
17982461
Acta Crystallogr D Biol Crystallogr. 2000 Jul;56(Pt 7):817-27
10930829