title: Radiation damage in macromolecular crystallography: what is it and why should we care?
abstract: Radiation damage inflicted during diffraction data collection in macromolecular crystallography has re-emerged in the last decade as a major experimental and computational challenge, as even for crystals held at 100 K it can result in severe data-quality degradation and the appearance in solved structures of artefacts which affect biological interpretations. Here, the observable symptoms and basic physical processes involved in radiation damage are described and the concept of absorbed dose as the basic metric against which to monitor the experimentally observed changes is outlined. Investigations into radiation damage in macromolecular crystallography are ongoing and the number of studies is rapidly increasing. The current literature on the subject is compiled as a resource for the interested researcher.
authors.affiliation: Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, England. elspeth.garman@bioch.ox.ac.uk
authors.forename: Elspeth F
authors.initials: EF
authors.lastname: Garman
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods*; D004307:Dose-Response Relationship, Radiation; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000032:analysis* / Q000737:chemistry; D014965:X-Rays
chemical_list: D011506:Proteins
references.citation: Protein Sci. 2005 Jun;14(6):1498-507
references.pmid: 15883191
references.citation: Biochemistry. 2008 Sep 2;47(35):9251-7
references.pmid: 18690706
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):393-408
references.pmid: 20382993
references.citation: Structure. 2003 Jan;11(1):13-9
references.pmid: 12517336
references.citation: J Synchrotron Radiat. 2004 Jan 1;11(Pt 1):113-6
references.pmid: 14646149
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Sep;62(Pt 9):1030-8
references.pmid: 16929104
references.citation: Acta Crystallogr A. 1988 Jul 1;44 ( Pt 4):443-8
references.pmid: 2978720
references.citation: J Synchrotron Radiat. 2002 Nov 1;9(Pt 6):355-60
references.pmid: 12409622
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Jun;60(Pt 6):1085-93
references.pmid: 15159568
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Apr;57(Pt 4):566-73
references.pmid: 11264586
references.citation: Curr Opin Struct Biol. 2003 Oct;13(5):545-51
references.pmid: 14568608
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 Sep;63(Pt 9):951-60
references.pmid: 17704563
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):96-101
references.pmid: 16369098
references.citation: J Mol Biol. 2008 Apr 25;378(2):353-61
references.pmid: 18353369
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Jun;60(Pt 6):1024-31
references.pmid: 15159561
references.citation: Structure. 2003 Feb;11(2):217-24
references.pmid: 12575941
references.citation: Methods Enzymol. 1997;276:183-203
references.pmid: 27799094
references.citation: Prog Biophys Mol Biol. 2005 Oct;89(2):173-205
references.pmid: 15910917
references.citation: J Synchrotron Radiat. 2002 Nov 1;9(Pt 6):342-6
references.pmid: 12409620
references.citation: Acta Crystallogr D Biol Crystallogr. 2008 Feb;64(Pt 2):158-66
references.pmid: 18219115
references.citation: J Synchrotron Radiat. 2008 Sep;15(Pt 5):458-62
references.pmid: 18728316
references.citation: J Am Chem Soc. 2004 Dec 29;126(51):16728-9
references.pmid: 15612703
references.citation: J Synchrotron Radiat. 2005 May;12(Pt 3):299-303
references.pmid: 15840914
references.citation: J Synchrotron Radiat. 2002 Nov 1;9(Pt 6):375-81
references.pmid: 12409625
references.citation: Acta Crystallogr D Biol Crystallogr. 2009 Apr;65(Pt 4):366-74
references.pmid: 19307718
references.citation: Structure. 2006 Jan;14(1):107-17
references.pmid: 16407070
references.citation: J Mol Biol. 2008 Dec 12;384(2):393-405
references.pmid: 18823996
references.citation: Nature. 2002 May 23;417(6887):463-8
references.pmid: 12024218
references.citation: J Synchrotron Radiat. 2009 Nov;16(Pt 6):872-9
references.pmid: 19844027
references.citation: J Synchrotron Radiat. 2005 May;12(Pt 3):261-7
references.pmid: 15840909
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):51-72
references.pmid: 17211072
references.citation: Acta Crystallogr D Biol Crystallogr. 2005 Sep;61(Pt 9):1289-98
references.pmid: 16131763
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):99-104
references.pmid: 17190816
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):73-83
references.pmid: 17211073
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):426-36
references.pmid: 20382996
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):109-15
references.pmid: 17211077
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Feb;62(Pt 2):125-32
references.pmid: 16421442
references.citation: Structure. 2006 Jul;14(7):1099-105
references.pmid: 16843891
references.citation: Biophys J. 2000 Jun;78(6):3178-85
references.pmid: 10827994
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):99-108
references.pmid: 17211076
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Apr;60(Pt 4):686-95
references.pmid: 15039557
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 Jul;63(Pt 7):759-68
references.pmid: 17582167
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Jan;57(Pt 1):69-81
references.pmid: 11134929
references.citation: J Biol Chem. 1958 Dec;233(6):1364-72
references.pmid: 13610844
references.citation: J Biol Chem. 2004 Jun 18;279(25):26417-24
references.pmid: 15026418
references.citation: J Synchrotron Radiat. 2002 Jul 1;9(Pt 4):198-201
references.pmid: 12091725
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10609-13
references.pmid: 19520834
references.citation: Protein Sci. 2001 Oct;10(10):1953-61
references.pmid: 11567086
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11742-7
references.pmid: 18701720
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):24-33
references.pmid: 17211069
references.citation: Science. 2000 Mar 3;287(5458):1615-22
references.pmid: 10698731
references.citation: J Synchrotron Radiat. 2005 May;12(Pt 3):285-91
references.pmid: 15840912
references.citation: Methods. 2004 Nov;34(3):415-23
references.pmid: 15325658
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):381-8
references.pmid: 20382991
references.citation: Acta Crystallogr B. 1988 Feb 1;44 ( Pt 1):22-6
references.pmid: 3271102
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12047-52
references.pmid: 16103362
references.citation: J Synchrotron Radiat. 2002 Nov 1;9(Pt 6):329-32
references.pmid: 12409618
references.citation: J Synchrotron Radiat. 2009 Mar;16(Pt 2):143-51
references.pmid: 19240326
references.citation: J Synchrotron Radiat. 2002 Nov 1;9(Pt 6):327-8
references.pmid: 12409617
references.citation: Curr Opin Struct Biol. 2006 Oct;16(5):624-9
references.pmid: 16938450
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):43-50
references.pmid: 17211071
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Apr;57(Pt 4):488-97
references.pmid: 11264577
references.citation: Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):623-8
references.pmid: 10639129
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 Apr;63(Pt 4):486-92
references.pmid: 17372353
references.citation: Structure. 2007 Dec;15(12):1531-41
references.pmid: 18073104
references.citation: J Mol Biol. 2009 Apr 17;387(5):1092-105
references.pmid: 19233199
references.citation: Nature. 1987 Dec 24-31;330(6150):772-3
references.pmid: 2827033
references.citation: J Synchrotron Radiat. 2009 Mar;16(Pt 2):183-90
references.pmid: 19240330
references.citation: Structure. 2000 Mar 15;8(3):315-28
references.pmid: 10745008
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):84-91
references.pmid: 17211074
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):409-19
references.pmid: 20382994
references.citation: Acta Crystallogr D Biol Crystallogr. 2009 Sep;65(Pt 9):1004-6
references.pmid: 19690379
references.citation: J Synchrotron Radiat. 2005 May;12(Pt 3):310-7
references.pmid: 15840916
references.citation: Acta Crystallogr D Biol Crystallogr. 2008 Mar;64(Pt 3):264-72
references.pmid: 18323621
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):4-10
references.pmid: 17211067
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 Apr;59(Pt 4):697-708
references.pmid: 12657789
references.citation: J Synchrotron Radiat. 2005 May;12(Pt 3):268-75
references.pmid: 15840910
references.citation: J Synchrotron Radiat. 2009 Mar;16(Pt 2):191-204
references.pmid: 19240331
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Nov;60(Pt 11):1958-63
references.pmid: 15502302
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4912-7
references.pmid: 16549763
references.citation: J Synchrotron Radiat. 2009 Mar;16(Pt 2):173-82
references.pmid: 19240329
references.citation: J Biol Chem. 2003 Jul 11;278(28):25919-25
references.pmid: 12707277
references.citation: J Mol Biol. 1976 May 5;103(1):1-13
references.pmid: 957422
references.citation: J Mol Biol. 1973 Mar 5;74(3):331-61
references.pmid: 4692855
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):92-8
references.pmid: 17211075
references.citation: J Mol Biol. 2002 Nov 29;324(3):469-81
references.pmid: 12445782
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Aug;58(Pt 8):1262-8
references.pmid: 12136136
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):32-47
references.pmid: 16369092
references.citation: Structure. 2004 Sep;12(9):1729-40
references.pmid: 15341736
references.citation: Structure. 2006 Apr;14(4):791-800
references.pmid: 16615919
references.citation: J Electron Spectros Relat Phenomena. 2009 Mar 1;170(1-3):4-12
references.pmid: 20463854
references.citation: J Am Chem Soc. 2009 Dec 23;131(50):18063-5
references.pmid: 19950947
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):58-64
references.pmid: 16369094
references.citation: J Synchrotron Radiat. 2002 Nov 1;9(Pt 6):347-54
references.pmid: 12409621
references.citation: J Synchrotron Radiat. 2009 Mar;16(Pt 2):205-16
references.pmid: 19240332
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):1-3
references.pmid: 17211066
references.citation: J Synchrotron Radiat. 2005 May;12(Pt 3):276-84
references.pmid: 15840911
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):34-42
references.pmid: 17211070
references.citation: Radiat Res. 1958 Dec;9(6):611-25
references.pmid: 13614647
references.citation: Acta Crystallogr D Biol Crystallogr. 2005 Sep;61(Pt 9):1227-37
references.pmid: 16131756
references.citation: Biochem J. 2008 Jun 1;412(2):257-64
references.pmid: 18215120
references.citation: J Mol Biol. 1976 Sep 25;106(3):889-93
references.pmid: 978739
references.citation: Acta Crystallogr D Biol Crystallogr. 2000 Nov;56(Pt 11):1413-20
references.pmid: 11053839
references.citation: J Mol Biol. 2004 Aug 20;341(4):1023-37
references.pmid: 15328615
references.citation: J Synchrotron Radiat. 2005 May;12(Pt 3):318-28
references.pmid: 15840917
references.citation: J Synchrotron Radiat. 2007 Jan;14(Pt 1):11-23
references.pmid: 17211068
references.citation: J Synchrotron Radiat. 2002 Nov 1;9(Pt 6):361-7
references.pmid: 12409623
references.citation: J Synchrotron Radiat. 2000 Sep 1;7(Pt 5):313-7
references.pmid: 16609214
references.citation: Trends Biochem Sci. 2005 Apr;30(4):213-9
references.pmid: 15817398
references.citation: Acta Crystallogr D Biol Crystallogr. 1994 Nov 1;50(Pt 6):874-7
references.pmid: 15299355
references.citation: J Mol Biol. 2007 May 4;368(3):833-44
references.pmid: 17368672
references.citation: J Synchrotron Radiat. 2005 May;12(Pt 3):257-60
references.pmid: 15840908
references.citation: Acta Crystallogr B Struct Crystallogr Cryst Chem. 1970 Jul 15;26(7):998-1004
references.pmid: 5536135
references.citation: Prog Nucleic Acid Res Mol Biol. 1988;35:95-125
references.pmid: 3065826
references.citation: J Biol Chem. 2006 Feb 24;281(8):4580-8
references.pmid: 16352605
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 May;59(Pt 5):903-9
references.pmid: 12777808
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):366-73
references.pmid: 20382989
references.citation: J Synchrotron Radiat. 2009 Mar;16(Pt 2):152-62
references.pmid: 19240327
references.citation: J Synchrotron Radiat. 2002 Nov 1;9(Pt 6):368-74
references.pmid: 12409624
references.citation: Acta Crystallogr D Biol Crystallogr. 2000 Mar;56(Pt 3):328-41
references.pmid: 10713520
references.citation: Protein Sci. 2005 Sep;14(9):2414-20
references.pmid: 16131664
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 Mar;63(Pt 3):302-9
references.pmid: 17327667
references.citation: J Synchrotron Radiat. 2009 Mar;16(Pt 2):163-72
references.pmid: 19240328
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Oct;55(Pt 10):1641-53
references.pmid: 10531512
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1094-9
references.pmid: 20080548
references.citation: J Synchrotron Radiat. 2005 May;12(Pt 3):304-9
references.pmid: 15840915
references.citation: J Mol Biol. 2003 Apr 18;328(1):289-301
references.pmid: 12684014
references.citation: Science. 2004 Dec 3;306(5702):1789-93
references.pmid: 15576622