Serial Synchrotron X-Ray Crystallography (SSX)

  • Kay DiederichsEmail author
  • Meitian Wang
Part of the Methods in Molecular Biology book series (MIMB, volume 1607)


Prompted by methodological advances in measurements with X-ray free electron lasers, it was realized in the last two years that traditional (or conventional) methods for data collection from crystals of macromolecular specimens can be complemented by synchrotron measurements on microcrystals that would individually not suffice for a complete data set. Measuring, processing, and merging many partial data sets of this kind requires new techniques which have since been implemented at several third-generation synchrotron facilities, and are described here. Among these, we particularly focus on the possibility of in situ measurements combined with in meso crystal preparations and data analysis with the XDS package and auxiliary programs.

Key words

Serial synchrotron crystallography (SSX) Microcrystal Lipidic cubic phase (LCP) In meso in situ Room temperature (RT) Cryogenic temperature Data collection Data quality Merging XDS XSCALE 



We thank Greta Assmann, Wolfgang Brehm, Martin Caffrey, Chia-Ying Huang, Vincent Olieric, Ezequiel Panepucci, Rangana Warshamanage, and all other members of the groups at the Swiss Light Source (Paul-Scherrer-Institute, Villigen, Switzerland), Trinity College (Dublin, Ireland) and University of Konstanz (Konstanz, Germany) for discussions and their contributions toward developing the methodology. We also thank Aaron Finke and Martin Caffrey for proofreading the manuscript and Rangana Warshamanage and Chia-Ying Huang for preparing the figures.


  1. 1.
    Arndt UW, Wonacott AJ (1977) The rotation method in crystallography. North-Holland Publishing Company, AmsterdamGoogle Scholar
  2. 2.
    Darwin CG (1914) XXXIV. The theory of X-ray reflexion. Philos Mag Ser 6 27:315–333CrossRefGoogle Scholar
  3. 3.
    Warren BE (1969) X-ray diffraction. Addison-Wesley Pub. Co., Reading, MAGoogle Scholar
  4. 4.
    Holton JM, Frankel KA (2010) The minimum crystal size needed for a complete diffraction data set. Acta Crystallogr D Biol Crystallogr 66:393–408PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Kendrew JC, Bodo G, Dintzis HM, Parrish RG, Wyckoff H, Phillips DC (1958) A three-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature 181:662–666PubMedCrossRefGoogle Scholar
  6. 6.
    Perutz MF, Rossmann MG, Cullis AF, Muirhead H, Will G (1960) Structure of hæmoglobin: a three-dimensional fourier synthesis at 5.5-Å. resolution, obtained by X-ray analysis. Nature 185:416–422PubMedCrossRefGoogle Scholar
  7. 7.
    Harrison SC, Olson AJ, Schutt CE, Winkler FK, Bricogne G (1978) Tomato bushy stunt virus at 2.9 A resolution. Nature 276:368–373PubMedCrossRefGoogle Scholar
  8. 8.
    Hendrickson WA (2000) Synchrotron crystallography. Trends Biochem Sci 25:637–643PubMedCrossRefGoogle Scholar
  9. 9.
    Hope H (1988) Cryocrystallography of biological macromolecules: a generally applicable method. Acta Crystallogr B 44:22–26PubMedCrossRefGoogle Scholar
  10. 10.
    Sliz P, Harrison SC, Rosenbaum G (2003) How does radiation damage in protein crystals depend on X-ray dose? Structure 11:13–19PubMedCrossRefGoogle Scholar
  11. 11.
    Cusack S, Belrhali H, Bram A, Burghammer M, Perrakis A, Riekel C (1998) Small is beautiful: protein micro-crystallography. Nat Struct Biol 5(Suppl):634–637PubMedCrossRefGoogle Scholar
  12. 12.
    Smith JL, Fischetti RF, Yamamoto M (2012) Micro-crystallography comes of age. Curr Opin Struct Biol 22:602–612PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Chapman HN, Fromme P, Barty A et al (2011) Femtosecond X-ray protein nanocrystallography. Nature 470:73–77PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Schlichting I (2015) Serial femtosecond crystallography: the first five years. IUCrJ 2:246–255PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Gavira JA (2015) Current trends in protein crystallization. Arch Biochem Biophys 602:3–11PubMedCrossRefGoogle Scholar
  16. 16.
    Liu W, Ishchenko A, Cherezov V (2014) Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography. Nat Protoc 9:2123–2134PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    DePonte DP, Weierstall U, Schmidt K, Warner J, Starodub D, Spence JCH, Doak RB (2008) Gas dynamic virtual nozzle for generation of microscopic droplet streams. J Phys D Appl Phys 41:195505CrossRefGoogle Scholar
  18. 18.
    Weierstall U, James D, Wang C et al (2014) Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat Commun 5:3309PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Botha S, Nass K, Barends TRM et al (2015) Room-temperature serial crystallography at synchrotron X-ray sources using slowly flowing free-standing high-viscosity microstreams. Acta Crystallogr D Biol Crystallogr 71:387–397PubMedCrossRefGoogle Scholar
  20. 20.
    Boutet S, Lomb L, Williams GJ et al (2012) High-resolution protein structure determination by serial femtosecond crystallography. Science 337:362–364PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Sierra RG, Laksmono H, Kern J et al (2012) Nanoflow electrospinning serial femtosecond crystallography. Acta Crystallogr D Biol Crystallogr 68:1584–1587PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Sugahara M, Mizohata E, Nango E et al (2015) Grease matrix as a versatile carrier of proteins for serial crystallography. Nat Methods 12:61–63PubMedCrossRefGoogle Scholar
  23. 23.
    Conrad CE, Basu S, James D et al (2015) A novel inert crystal delivery medium for serial femtosecond crystallography. IUCrJ 2:421–430PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Liu W, Wacker D, Gati C et al (2013) Serial femtosecond crystallography of G protein-coupled receptors. Science 342:1521–1524PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Fenalti G, Zatsepin NA, Betti C et al (2015) Structural basis for bifunctional peptide recognition at human δ-opioid receptor. Nat Struct Mol Biol 22:265–268PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Zhang H, Unal H, Gati C et al (2015) Structure of the angiotensin receptor revealed by serial femtosecond crystallography. Cell 161:833–844PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Kang Y, Zhou XE, Gao X et al (2015) Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523:561–567PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Nogly P, James D, Wang D, White TA, Shilova A, Nelson G, Liu H, Johansson L (2015) Lipidic cubic phase serial millisecond crystallography using synchrotron radiation. IUCrJ 2:168–176PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Stellato F, Oberthür D, Liang M et al (2014) Room-temperature macromolecular serial crystallography using synchrotron radiation. IUCrJ 1:204–212PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Roessler CG, Agarwal R, Allaire M et al (2016) Acoustic injectors for drop-on-demand serial femtosecond crystallography. Structure 24:631–640PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Roessler CG, Kuczewski A, Stearns R, Ellson R, Olechno J, Orville AM, Allaire M, Soares AS, Héroux A (2013) Acoustic methods for high-throughput protein crystal mounting at next-generation macromolecular crystallographic beamlines. J Synchrotron Radiat 20:805–808PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Soares AS, Mullen JD, Parekh RM, McCarthy GS, Roessler CG, Jackimowicz R, Skinner JM, Orville AM, Allaire M, Sweet RM (2014) Solvent minimization induces preferential orientation and crystal clustering in serial micro-crystallography on micro-meshes, in situ plates and on a movable crystal conveyor belt. J Synchrotron Radiat 21:1231–1239PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Tsujino S, Tomizaki T (2016) Ultrasonic acoustic levitation for fast frame rate X-ray protein crystallography at room temperature. Sci Rep 6:25558PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Hunter MS, Segelke B, Messerschmidt M et al (2014) Fixed-target protein serial microcrystallography with an X-ray free electron laser. Sci Rep 4:6026PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Cohen AE, Soltis SM, González A et al (2014) Goniometer-based femtosecond crystallography with X-ray free electron lasers. Proc Natl Acad Sci U S A 111:17122–17127PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Hirata K, Shinzawa-Itoh K, Yano N et al (2014) Determination of damage-free crystal structure of an X-ray-sensitive protein using an XFEL. Nat Methods 11:734–736PubMedCrossRefGoogle Scholar
  37. 37.
    Wierman JL, Alden JS, Kim CU, McEuen PL, Gruner SM (2013) Graphene as a protein crystal mounting material to reduce background scatter. J Appl Crystallogr 46:1501–1507PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Warren AJ, Crawshaw AD, Trincao J, Aller P, Alcock S, Nistea I, Salgado PS, Evans G (2015) In vacuo X-ray data collection from graphene-wrapped protein crystals. Acta Crystallogr D Biol Crystallogr 71:2079–2088PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Sui S, Wang Y, Kolewe KW, Srajer V, Henning R, Schiffman JD, Dimitrakopoulos C, Perry SL (2016) Graphene-based microfluidics for serial crystallography. Lab Chip. Advance article. doi: 10.1039/C6LC00451B
  40. 40.
    Zarrine-Afsar A, Barends TRM, Müller C, Fuchs MR, Lomb L, Schlichting I, Miller RJD (2012) Crystallography on a chip. Acta Crystallogr D Biol Crystallogr 68:321–323PubMedCrossRefGoogle Scholar
  41. 41.
    Murray TD, Lyubimov AY, Ogata CM, Vo H, Uervirojnangkoorn M, Brunger AT, Berger JM (2015) A high-transparency, micro-patternable chip for X-ray diffraction analysis of microcrystals under native growth conditions. Acta Crystallogr D Biol Crystallogr 71:1987–1997PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Roedig P, Vartiainen I, Duman R et al (2015) A micro-patterned silicon chip as sample holder for macromolecular crystallography experiments with minimal background scattering. Sci Rep 5:10451PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Lyubimov AY, Murray TD, Koehl A et al (2015) Capture and X-ray diffraction studies of protein microcrystals in a microfluidic trap array. Acta Crystallogr D Biol Crystallogr 71:928–940PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Baxter EL, Aguila L, Alonso-Mori R et al (2016) High-density grids for efficient data collection from multiple crystals. Acta Crystallogr D Biol Crystallogr 72:2–11CrossRefGoogle Scholar
  45. 45.
    Coquelle N, Brewster AS, Kapp U, Shilova A, Weinhausen B, Burghammer M, Colletier JP (2015) Raster-scanning serial protein crystallography using micro- and nano-focused synchrotron beams. Acta Crystallogr D Biol Crystallogr 71:1184–1196PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Coulibaly F, Chiu E, Ikeda K, Gutmann S, Haebel PW, Schulze-Briese C, Mori H, Metcalf P (2007) The molecular organization of cypovirus polyhedra. Nature 446:97–101PubMedCrossRefGoogle Scholar
  47. 47.
    Cherezov V, Hanson MA, Griffith MT, Hilgart MC, Sanishvili R, Nagarajan V, Stepanov S, Fischetti RF, Kuhn P, Stevens RC (2009) Rastering strategy for screening and centring of microcrystal samples of human membrane proteins with a sub-10 microm size X-ray synchrotron beam. J R Soc Interface 6(Suppl 5):S587–S597PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Ji X, Sutton G, Evans G, Axford D, Owen R, Stuart DI (2010) How baculovirus polyhedra fit square pegs into round holes to robustly package viruses. EMBO J 29:505–514PubMedCrossRefGoogle Scholar
  49. 49.
    Axford D, Ji X, Stuart DI, Sutton G (2014) In cellulo structure determination of a novel cypovirus polyhedrin. Acta Crystallogr D Biol Crystallogr 70:1435–1441PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Zander U, Bourenkov G, Popov AN, de Sanctis D, Svensson O, AA MC, Round E, Gordeliy V, Mueller-Dieckmann C, Leonard GA (2015) MeshAndCollect: an automated multi-crystal data-collection workflow for synchrotron macromolecular crystallography beamlines. Acta Crystallogr D Biol Crystallogr 71:2328–2343PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Boudes M, Garriga D, Fryga A, Caradoc-Davies T, Coulibaly F (2016) A pipeline for structure determination of ıt in vivo-grown crystals using ıt in cellulo diffraction. Acta Crystallogr D Biol Crystallogr 72:576–585CrossRefGoogle Scholar
  52. 52.
    Gati C, Bourenkov G, Klinge M et al (2014) Serial crystallography on in vivo grown microcrystals using synchrotron radiation. IUCrJ 1:87–94PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Li L, Ismagilov RF (2010) Protein crystallization using microfluidic technologies based on valves, droplets, and SlipChip. Annu Rev Biophys 39:139–158PubMedCrossRefGoogle Scholar
  54. 54.
    Kisselman G, Qiu W, Romanov V, Thompson CM, Lam R, Battaile KP, Pai EF, Chirgadze NY (2011) X-CHIP: an integrated platform for high-throughput protein crystallization and on-the-chip X-ray diffraction data collection. Acta Crystallogr D Biol Crystallogr 67:533–539PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Dhouib K, Khan Malek C, Pfleging W et al (2009) Microfluidic chips for the crystallization of biomacromolecules by counter-diffusion and on-chip crystal X-ray analysis. Lab Chip 9:1412–1421PubMedCrossRefGoogle Scholar
  56. 56.
    Pinker F, Brun M, Morin P et al (2013) ChipX: a novel microfluidic chip for counter-diffusion crystallization of biomolecules and in situ crystal analysis at room temperature. Cryst Growth Des 13:3333–3340CrossRefGoogle Scholar
  57. 57.
    Perry SL, Guha S, Pawate AS, Bhaskarla A, Agarwal V, Nair SK, Kenis PJA (2013) A microfluidic approach for protein structure determination at room temperature via on-chip anomalous diffraction. Lab Chip 13:3183–3187PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Khvostichenko DS, Schieferstein JM, Pawate AS, Laible PD, Kenis PJA (2014) X-ray transparent microfluidic chip for mesophase-based crystallization of membrane proteins and on-chip structure determination. Cryst Growth Des 14:4886–4890PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Heymann M, Opthalage A, Wierman JL, Akella S, Szebenyi DME, Gruner SM, Fraden S (2014) Room-temperature serial crystallography using a kinetically optimized microfluidic device for protein crystallization and on-chip X-ray diffraction. IUCrJ 1:349–360PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Jacquamet L, Ohana J, Joly J et al (2004) Automated analysis of vapor diffusion crystallization drops with an X-ray beam. Structure 12:1219–1225PubMedCrossRefGoogle Scholar
  61. 61.
    Bingel-Erlenmeyer R, Olieric V, Grimshaw JPA et al (2011) SLS crystallization platform at beamline X06DA—a fully automated pipeline enabling in situ X-ray diffraction screening. Cryst Growth Des 11:916–923CrossRefGoogle Scholar
  62. 62.
    Axford D, Owen RL, Aishima J et al (2012) In situ macromolecular crystallography using microbeams. Acta Crystallogr D Biol Crystallogr 68:592–600PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Axford D, Foadi J, Hu N-J, Choudhury HG, Iwata S, Beis K, Evans G, Alguel Y (2015) Structure determination of an integral membrane protein at room temperature from crystals in situ. Acta Crystallogr D Biol Crystallogr 71:1228–1237PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Gelin M, Delfosse V, Allemand F, Hoh F, Sallaz-Damaz Y, Pirocchi M, Bourguet W, Ferrer JL, Labesse G, Guichou JF (2015) Combining “dry” co-crystallization and in situ diffraction to facilitate ligand screening by X-ray crystallography. Acta Crystallogr D Biol Crystallogr 71:1777–1787PubMedCrossRefGoogle Scholar
  65. 65.
    Axford D, Aller P, Sanchez-Weatherby J, Sandy J (2016) Applications of thin-film sandwich crystallization platforms. Acta Crystallogr F Struct Biol Commun 72:313–319PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Cipriani F, Röwer M, Landret C, Zander U, Felisaz F, Márquez JA (2012) CrystalDirect: a new method for automated crystal harvesting based on laser-induced photoablation of thin films. Acta Crystallogr D Biol Crystallogr 68:1393–1399PubMedCrossRefGoogle Scholar
  67. 67.
    Zander U, Hoffmann G, Cornaciu I et al (2016) Automated harvesting and processing of protein crystals through laser photoablation. Acta Crystallogr D Biol Crystallogr 72:454–466CrossRefGoogle Scholar
  68. 68.
    Caffrey M (2015) A comprehensive review of the lipid cubic phase or in meso method for crystallizing membrane and soluble proteins and complexes. Acta Crystallogr F Struct Biol Commun 71:3–18PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Huang CY, Olieric V, Ma P, Panepucci E, Diederichs K, Wang M, Caffrey M (2015) In meso in situ serial X-ray crystallography of soluble and membrane proteins. Acta Crystallogr D Biol Crystallogr 71:1238–1256PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Huang CY, Olieric V, Ma P et al (2016) In meso in situ serial X-ray crystallography of soluble and membrane proteins at cryogenic temperatures. Acta Crystallogr D Biol Crystallogr 72:93–112CrossRefGoogle Scholar
  71. 71.
    Fraser JS, van den Bedem H, Samelson AJ, Lang PT, Holton JM, Echols N, Alber T (2011) Accessing protein conformational ensembles using room-temperature X-ray crystallography. Proc Natl Acad Sci U S A 108:16247–16252PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Keedy DA, Kenner LR, Warkentin M et al (2015) Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography. Elife 4:e07574PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Leal RMF, Bourenkov G, Russi S, Popov AN (2013) A survey of global radiation damage to 15 different protein crystal types at room temperature: a new decay model. J Synchrotron Radiat 20:14–22PubMedCrossRefGoogle Scholar
  74. 74.
    Owen RL, Paterson N, Axford D, Aishima J, Schulze-Briese C, Ren J, Fry EE, Stuart DI, Evans G (2014) Exploiting fast detectors to enter a new dimension in room-temperature crystallography. Acta Crystallogr D Biol Crystallogr 70:1248–1256PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Henderson R (1990) Cryo-protection of protein crystals against radiation damage in electron and X-ray diffraction. Proc R Soc Lond B 241:6–8CrossRefGoogle Scholar
  76. 76.
    Owen RL, Rudiño-Piñera E, Garman EF (2006) Experimental determination of the radiation dose limit for cryocooled protein crystals. Proc Natl Acad Sci U S A 103:4912–4917PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Evans G, Axford D, Owen RL (2011) The design of macromolecular crystallography diffraction experiments. Acta Crystallogr D Biol Crystallogr 67:261–270PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Mueller M, Wang M, Schulze-Briese C (2012) Optimal fine φ-slicing for single-photon-counting pixel detectors. Acta Crystallogr D Biol Crystallogr 68:42–56PubMedCrossRefGoogle Scholar
  79. 79.
    Dauter Z (1999) Data-collection strategies. Acta Crystallogr D Biol Crystallogr 55:1703–1717PubMedCrossRefGoogle Scholar
  80. 80.
    Bourenkov GP, Popov AN (2006) A quantitative approach to data-collection strategies. Acta Crystallogr D Biol Crystallogr 62:58–64PubMedCrossRefGoogle Scholar
  81. 81.
    Borek D, Minor W, Otwinowski Z (2003) Measurement errors and their consequences in protein crystallography. Acta Crystallogr D Biol Crystallogr 59:2031–2038PubMedCrossRefGoogle Scholar
  82. 82.
    Liu ZJ, Chen L, Wu D, Ding W, Zhang H, Zhou W, Fu ZQ, Wang BC (2011) A multi-dataset data-collection strategy produces better diffraction data. Acta Crystallogr A 67:544–549PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Weinert T, Olieric V, Waltersperger S et al (2015) Fast native-SAD phasing for routine macromolecular structure determination. Nat Methods 12:131–133PubMedCrossRefGoogle Scholar
  84. 84.
    Brockhauser S, White KI, AA MC, RBG R (2011) Translation calibration of inverse-kappa goniometers in macromolecular crystallography. Acta Crystallogr A 67:219–228PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Waltersperger S, Olieric V, Pradervand C et al (2015) PRIGo: a new multi-axis goniometer for macromolecular crystallography. J Synchrotron Radiat 22:895–900PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Liu Q, Dahmane T, Zhang Z, Assur Z, Brasch J, Shapiro L, Mancia F, Hendrickson WA (2012) Structures from anomalous diffraction of native biological macromolecules. Science 336:1033PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Olieric V, Weinert T, Finke AD et al (2016) Data-collection strategy for challenging native SAD phasing. Acta Crystallogr D Biol Crystallogr 72:421–429CrossRefGoogle Scholar
  88. 88.
    Liu Q, Hendrickson WA (2015) Crystallographic phasing from weak anomalous signals. Curr Opin Struct Biol 34:99–107PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Ayyer K, Philipp HT, Tate MW, Wierman JL, Elser V, Gruner SM (2015) Determination of crystallographic intensities from sparse data. IUCrJ 2:29–34PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Holton JM (2009) A beginner’s guide to radiation damage. J Synchrotron Radiat 16:133–142PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Kabsch W (2010) Xds. Acta Crystallogr D Biol Crystallogr 66:125–132PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Kabsch W (2010) Integration, scaling, space-group assignment and post-refinement. Acta Crystallogr D Biol Crystallogr 66:133–144PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Battye TGG, Kontogiannis L, Johnson O, Powell HR, Leslie AGW (2011) iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM. Acta Crystallogr D Biol Crystallogr 67:271–281PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Otwinowski Z, Minor W (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol 276:307–326CrossRefGoogle Scholar
  95. 95.
    Brehm W, Diederichs K (2013) Breaking the indexing ambiguity in serial crystallography. Acta Crystallogr D Biol Crystallogr 70:101–109PubMedCrossRefGoogle Scholar
  96. 96.
    Arndt UW, Crowther RA, Mallett JF (1968) A computer-linked cathode-ray tube microdensitometer for X-ray crystallography. J Sci Instrum 1:510–516PubMedCrossRefGoogle Scholar
  97. 97.
    Diederichs K, Karplus A (1997) Improved R-factors. Nat Struct Biol 4:269–275PubMedCrossRefGoogle Scholar
  98. 98.
    Krojer T, von Delft F (2011) Assessment of radiation damage behaviour in a large collection of empirically optimized datasets highlights the importance of unmeasured complicating effects. J Synchrotron Radiat 18:387–397PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Karplus PA, Diederichs K (2012) Linking crystallographic model and data quality. Science 336:1030–1033PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Diederichs K, Karplus PA (2013) Better models by discarding data? Acta Crystallogr D Biol Crystallogr 69:1215–1222PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Karplus PA, Diederichs K (2015) Assessing and maximizing data quality in macromolecular crystallography. Curr Opin Struct Biol 34:60–68PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Assmann G, Brehm W, Diederichs K (2016) Identification of rogue datasets in serial crystallography. J Appl Crystallogr 49:1021–1028PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Sheldrick GM (2010) Experimental phasing with SHELXC/D/E: combining chain tracing with density modification. Acta Crystallogr D Biol Crystallogr 66:479–485PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Adams PD, Afonine PV, Bunkóczi G et al (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66:213–221PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Department of BiologyUniversität KonstanzKonstanzGermany
  2. 2.Swiss Light SourcePaul Scherrer InstituteVilligenSwitzerland

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