title: Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination.
abstract: The number of macromolecular structures deposited in the Protein Data Bank now approaches 100,000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation.
authors.affiliation: Protein Structure Section, Macromolecular Crystallography Laboratory, NCI at Frederick, Frederick, MD, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wlodawer
authors.forename: Wladek
authors.initials: W
authors.lastname: Minor
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Dauter
authors.forename: Mariusz
authors.initials: M
authors.lastname: Jaskolski
mesh_terms: D003461:Crystallography / Q000379:methods* / Q000706:statistics & numerical data; D018360:Crystallography, X-Ray / Q000379:methods / Q000706:statistics & numerical data; D030562:Databases, Protein; D008958:Models, Molecular; D015394:Molecular Structure; D010936:Plant Extracts; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D012984:Software; D055672:Static Electricity
chemical_list: C112288:LI 1370; D010936:Plant Extracts; D011506:Proteins
keywords: data collection and processing; electron density maps; protein crystallography; structure quality; structure refinement; structure solution; structure validation
references.citation: J Mol Biol. 1999 May 28;289(1):83-92
references.pmid: 10339407
references.citation: Elife. 2012 Dec 18;1:e00311
references.pmid: 23251785
references.citation: Nature. 1989 Feb 9;337(6207):576-9
references.pmid: 2536902
references.citation: Science. 2012 May 25;336(6084):1033-7
references.pmid: 22628655
references.citation: Nat Struct Biol. 1999 May;6(5):458-63
references.pmid: 10331874
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Apr;62(Pt 4):439-50
references.pmid: 16552146
references.citation: Nature. 1981 Mar 12;290(5802):107-113
references.pmid: 28769131
references.citation: Nature. 1989 Feb 16;337(6208):615-20
references.pmid: 2645523
references.citation: Nat Struct Mol Biol. 2011 Sep 18;18(10):1175-7
references.pmid: 21926992
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):96-101
references.pmid: 16369098
references.citation: Science. 2012 May 25;336(6084):1030-3
references.pmid: 22628654
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 Mar;59(Pt 3):615-7
references.pmid: 12595742
references.citation: Science. 1989 May 12;244(4905):702-5
references.pmid: 17740342
references.citation: Nature. 2002 May 30;417(6888):515-22
references.pmid: 12037559
references.citation: J Mol Biol. 1984 Dec 5;180(2):385-98
references.pmid: 6392571
references.citation: Nature. 1983 May 19-25;303(5914):195-6
references.pmid: 6843668
references.citation: Nat Methods. 2007 Nov;4(11):927-9
references.pmid: 17952087
references.citation: Methods Enzymol. 1997;276:344-58
references.pmid: 9048378
references.citation: Comput Biol Chem. 2013 Oct;46:8-15
references.pmid: 23751279
references.citation: PLoS One. 2012;7(10):e46039
references.pmid: 23056231
references.citation: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W615-9
references.pmid: 15215462
references.citation: Science. 2001 Sep 7;293(5536):1793-800
references.pmid: 11546864
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Jul;57(Pt 7):990-5
references.pmid: 11418767
references.citation: Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67
references.pmid: 21460454
references.citation: Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):282-92
references.pmid: 21460446
references.citation: Science. 1989 Aug 11;245(4918):616-21
references.pmid: 2548279
references.citation: Nature. 1960 Feb 13;185(4711):416-22
references.pmid: 18990801
references.citation: J Synchrotron Radiat. 2010 Jul;17(4):433-44
references.pmid: 20567074
references.citation: Nature. 2000 Sep 21;407(6802):327-39
references.pmid: 11014182
references.citation: Acta Crystallogr D Biol Crystallogr. 2008 Jan;64(Pt 1):119-24
references.pmid: 18094475
references.citation: Acta Crystallogr D Biol Crystallogr. 2012 Jan;68(Pt 1):42-56
references.pmid: 22194332
references.citation: Cell Mol Life Sci. 2006 Feb;63(3):285-300
references.pmid: 16389451
references.citation: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references.pmid: 15299926
references.citation: Nat Struct Biol. 2001 Aug;8(8):663-4
references.pmid: 11473252
references.citation: Nature. 2007 Nov 15;450(7168):383-7
references.pmid: 17952055
references.citation: Nature. 2006 Sep 14;443(7108):180-5
references.pmid: 16943773
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):611-20
references.pmid: 17452786
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 Sep;63(Pt 9):941-50
references.pmid: 17704562
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Oct;58(Pt 10 Pt 2):1772-9
references.pmid: 12351820
references.citation: Acta Crystallogr D Biol Crystallogr. 2012 Jun;68(Pt 6):713-23
references.pmid: 22683794
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: J Mol Biol. 1987 Jan 5;193(1):145-56
references.pmid: 2438420
references.citation: Nature. 2009 Dec 3;462(7273):669-73
references.pmid: 19956261
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2240-9
references.pmid: 15572777
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Mar;58(Pt 3):494-506
references.pmid: 11856836
references.citation: J Mol Biol. 1970 Nov 28;54(1):121-4
references.pmid: 5531171
references.citation: Proc Natl Acad Sci U S A. 1976 Jan;73(1):128-32
references.pmid: 1061106
references.citation: Acta Crystallogr B. 2002 Jun;58(Pt 3 Pt 1):380-8
references.pmid: 12037359
references.citation: Acta Crystallogr D Biol Crystallogr. 2005 Apr;61(Pt 4):449-57
references.pmid: 15805600
references.citation: Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1314-32
references.pmid: 23793158
references.citation: Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1447-62
references.pmid: 23897468
references.citation: Acta Crystallogr D Biol Crystallogr. 2013 May;69(Pt 5):838-42
references.pmid: 23633593
references.citation: Acta Crystallogr D Biol Crystallogr. 2005 Jul;61(Pt 7):967-75
references.pmid: 15983420
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3183-8
references.pmid: 17360626
references.citation: Science. 2012 Jul 20;337(6092):362-4
references.pmid: 22653729
references.citation: Neuron. 2007 May 24;54(4):511-33
references.pmid: 17521566
references.citation: Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):1865-6
references.pmid: 24100306
references.citation: Nature. 1992 Jan 30;355(6359):472-5
references.pmid: 18481394
references.citation: Nature. 2011 May 26;473(7348):540-3
references.pmid: 21532589
references.citation: Nucleic Acids Res. 2011 Aug;39(14):6238-48
references.pmid: 21459852
references.citation: Nature. 2003 May 1;423(6935):33-41
references.pmid: 12721618
references.citation: Acta Crystallogr D Biol Crystallogr. 2008 Jan;64(Pt 1):125-32
references.pmid: 18094476
references.citation: Curr Opin Struct Biol. 2010 Oct;20(5):587-97
references.pmid: 20810277
references.citation: Cell. 2000 Sep 1;102(5):615-23
references.pmid: 11007480
references.citation: Methods Enzymol. 1985;115:252-70
references.pmid: 3841182
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Sep;62(Pt 9):1002-11
references.pmid: 16929101
references.citation: J Am Chem Soc. 2008 Jun 11;130(23):7235-7
references.pmid: 18479128
references.citation: J Cheminform. 2013 Jul 29;5(1):36
references.pmid: 23895374
references.citation: Structure. 2012 Oct 10;20(10):1715-25
references.pmid: 22940582
references.citation: J Mol Biol. 1977 May 25;112(3):535-42
references.pmid: 875032
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Apr 1;68(Pt 4):366-76
references.pmid: 22505400
references.citation: Biochemistry. 2012 Sep 25;51(38):7638-50
references.pmid: 22928725
references.citation: Curr Opin Struct Biol. 2013 Jun;23(3):409-16
references.pmid: 23578532
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Aug;62(Pt 8):859-66
references.pmid: 16855301
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: Nat Struct Biol. 1997 Apr;4(4):269-75
references.pmid: 9095194
references.citation: Acta Crystallogr D Biol Crystallogr. 2012 Sep;68(Pt 9):1140-51
references.pmid: 22948915
references.citation: Nat Struct Mol Biol. 2011 Feb;18(2):227-9
references.pmid: 21258323
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 May;57(Pt 5):649-63
references.pmid: 11320305
references.citation: Science. 2000 Aug 11;289(5481):905-20
references.pmid: 10937989
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
references.pmid: 20124702
references.citation: Proc Natl Acad Sci U S A. 1975 Mar;72(3):777-9
references.pmid: 1055377
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
references.pmid: 12393927
references.citation: Acta Crystallogr D Biol Crystallogr. 2009 Oct;65(Pt 10):1089-97
references.pmid: 19770506
references.citation: Expert Opin Drug Discov. 2011 Aug 1;6(8):771-782
references.pmid: 21779303
references.citation: Science. 1991 Oct 4;254(5028):51-8
references.pmid: 1925561
references.citation: Curr Opin Struct Biol. 2011 Aug;21(4):567-72
references.pmid: 21782416
references.citation: Nature. 1958 Mar 8;181(4610):662-6
references.pmid: 13517261
references.citation: Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14
references.pmid: 23793146
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):58-64
references.pmid: 16369094
references.citation: Acta Crystallogr D Biol Crystallogr. 2000 Mar;56(Pt 3):249-65
references.pmid: 10713511
references.citation: Acta Crystallogr D Biol Crystallogr. 2000 Feb;56(Pt 2):232-7
references.pmid: 10666615
references.citation: Methods Enzymol. 2003;374:22-37
references.pmid: 14696367
references.citation: FEBS Lett. 1982 Sep 6;146(1):217-20
references.pmid: 6754439
references.citation: Nature. 1991 Dec 5;354(6352):411-4
references.pmid: 1956407
references.citation: J Mol Biol. 2000 Feb 4;295(5):1237-49
references.pmid: 10653700
references.citation: Acta Crystallogr D Biol Crystallogr. 2011 Aug;67(Pt 8):699-706
references.pmid: 21795811
references.citation: FEBS J. 2008 Jan;275(1):1-21
references.pmid: 18034855
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Sep;58(Pt 9):1448-61
references.pmid: 12198301
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Feb 1;69(Pt 2):195-200
references.pmid: 23385767
references.citation: Structure. 2009 Oct 14;17(10):1316-25
references.pmid: 19836332
references.citation: J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
references.pmid: 19461840
references.citation: Nature. 2007 Aug 9;448(7154):E1-2; discussion E2-3
references.pmid: 17687277
references.citation: EMBO J. 1990 May;9(5):1665-72
references.pmid: 2184035
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 May;59(Pt 5):903-9
references.pmid: 12777808
references.citation: Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22
references.pmid: 18156677
references.citation: Science. 1988 Jul 1;241(4861):71-4
references.pmid: 3133767
references.citation: Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):484-96
references.pmid: 22505269
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 Jul;59(Pt 7):1145-53
references.pmid: 12832757
references.citation: Acta Crystallogr D Biol Crystallogr. 2013 May;69(Pt 5):796-803
references.pmid: 23633588
references.citation: Acta Crystallogr D Biol Crystallogr. 2011 Nov;67(Pt 11):907-14
references.pmid: 22101816
references.citation: Structure. 1995 Jun 15;3(6):535-40
references.pmid: 8590014