Quantitative Biology

, Volume 4, Issue 3, pp 159–176 | Cite as

XFEL data analysis for structural biology

Review

Abstract

X-ray Free Electron Lasers (XFELs) have advanced research in structure biology, by exploiting their ultra-short and bright X-ray pulses. The resulting “diffraction before destruction” experimental approach allows data collection to outrun radiation damage, a crucial factor that has often limited resolution in the structure determination of biological molecules. Since the first hard X-ray laser (the Linac Coherent Light Source (LCLS) at SLAC) commenced operation in 2009, serial femtosecond crystallography (SFX) has rapidly matured into a method for the structural analysis of nano- and micro-crystals. At the same time, single particle structure determination by coherent diffractive imaging, with one particle (such as a virus) per shot, has been under intense development. In this review we describe these applications of X-ray lasers in structural biology, with a focus particularly on aspects of data analysis for the computational research community.We summarize the key problems in data analysis and model reconstruction, and provide perspectives on future research using computational methods.

Keywords

X-ray Free Electron Laser single particle scattering serial crystallography phase retrieval orientation recovery 

References

  1. 1.
    Solem, J. C. (1986) Imaging biological specimens with high-intensity soft x rays. J. Opt. Soc. Am. B, 3, 1551–1565CrossRefGoogle Scholar
  2. 2.
    Neutze, R., Wouts, R., van der Spoel, D., Weckert, E. and Hajdu, J. (2000) Potential for biomolecular imaging with femtosecond X-ray pulses. Nature, 406, 752–757CrossRefPubMedGoogle Scholar
  3. 3.
    Seibert, M. M., Ekeberg, T., Maia, F. R. N. C., Svenda, M., Andreasson, J., Jö nsson, O., Odic, D., Iwan, B., Rocker, A., Westphal, D., et al. (2011) Single mimivirus particles intercepted and imaged with an X-ray laser. Nature, 470, 78–81CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Emma, P., Akre, R., Arthur, J., Bionta, R., Bostedt, C., Bozek, J., Brachmann, A., Bucksbaum, P., Coffee, R., Decker, F.-J., et al. (2010) First lasing and operation of an angstrom-wavelength free-electron laser. Nat. Photonics, 4, 641–647CrossRefGoogle Scholar
  5. 5.
    Chapman, H. N., Fromme, P., Barty, A., White, T. A., Kirian, R. A., Aquila, A., Hunter, M. S., Schulz, J., DePonte, D. P., Weierstall, U., et al. (2011) Femtosecond X-ray protein nanocrystallography. Nature, 470, 73–77CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Liu, W., Wacker, D., Gati, C., Han, G.W., James, D., Wang, D., Nelson, G., Weierstall, U., Katritch, V., Barty, A., et al. (2013) Serial femtosecond crystallography of G protein-coupled receptors. Science, 342, 1521–1524CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Redecke, L., Nass, K., DePonte, D. P., White, T. A., Rehders, D., Barty, A., Stellato, F., Liang, M., Barends, T. R., Boutet, S., et al. (2013) Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser. Science, 339, 227–230CrossRefPubMedGoogle Scholar
  8. 8.
    Spence, J. C. H. and Doak, R. B. (2004) Single molecule diffraction. Phys. Rev. Lett., 92, 198102CrossRefPubMedGoogle Scholar
  9. 9.
    Spence, J. C. H., Weierstall, U. and Chapman, H. N. (2012) X-ray lasers for structural and dynamic biology. Rep. Prof. Phys., 75, 102601CrossRefGoogle Scholar
  10. 10.
    Schlichting, I. (2015) Serial femtosecond crystallography: the first five years. IUCrJ, 2, 246–255CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Wang, D., Weierstall, U., Pollack, L. and Spence, J. (2014) Doublefocusing mixing jet for XFEL study of chemical kinetics. J. Synchrotron Radiat., 21, 1364–1366CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Mayer, G. and Heckel, A. (2006) Biologically active molecules with a “light switch”. Angew. Chem. Int. Ed. Engl., 45, 4900–4921CrossRefPubMedGoogle Scholar
  13. 13.
    Kam, Z. (1977) Determination of macromolecular structure in solution by spatial correlation of scattering fluctuations. Macromolecules, 10, 927–934CrossRefGoogle Scholar
  14. 14.
    Kam, Z., Koch, M. H. J. and Bordas, J. (1981) Fluctuation x-ray scattering from biological particles in frozen solution by using synchrotron radiation. Proc. Natl. Acad. Sci. USA, 78, 3559–3562CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Saldin, D. K., Poon, H. C., Bogan, M. J., Marchesini, S., Shapiro, D. A., Kirian, R. A., Weierstall, U. and Spence, J. C. (2011) New light on disordered ensembles: ab initio structure determination of one particle from scattering fluctuations of many copies. Phys. Rev. Lett., 106, 115501CrossRefPubMedGoogle Scholar
  16. 16.
    Liu, H., Poon, B. K., Saldin, D. K., Spence, J. C. H. and Zwart, P. H. (2013) Three-dimensional single-particle imaging using angular correlations from X-ray laser data. Acta Crystallogr. A, Foundations of crystallography, 69, 365–373CrossRefPubMedGoogle Scholar
  17. 17.
    Pedrini, B., Menzel, A., Guizar-Sicairos, M., Guzenko, V. A., Gorelick, S., David, C., Patterson B. D., and Abela, R. (2013). Two-dimensional structure from random multiparticle X-ray scattering images using cross-correlations. Nat. Commun., 4, 1647Google Scholar
  18. 18.
    Kurta, R. P., Dronyak, R., Altarelli, M., Weckert, E. and Vartanyants, I. A. (2013) Solution of the phase problem for coherent scattering from a disordered system of identical particles. New J. Phys., 15, 013059CrossRefGoogle Scholar
  19. 19.
    Saldin, D. K., Poon, H.-C., Schwander, P., Uddin, M. and Schmidt, M. (2011) Reconstructing an icosahedral virus from single-particle diffraction experiments. Opt. Express, 19, 17318–17335CrossRefPubMedGoogle Scholar
  20. 20.
    Donatelli, J. J., Zwart, P. H. and Sethian, J. A. (2015) Iterative phasing for fluctuation X-ray scattering. Proc. Natl. Acad. Sci. USA, 112, 10286–10291CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Barty, A., Kirian, R. A., Maia, F. R. N. C., Hantke, M., Yoon, C. H., White, T. A. and Chapman, H. (2014) Cheetah: software for highthroughput reduction and analysis of serial femtosecond X-ray diffraction data. J. Appl. Cryst., 47, 1118–1131CrossRefGoogle Scholar
  22. 22.
    Foucar, L., Barty, A., Coppola, N., Hartmann, R., Holl, P., Hoppe, U., Kassemeyer, S., Kimmel, N., Kü pper, J., Scholz, M., et al. (2012) CASS—CFEL-ASG software suite. Comput. Phys. Commun., 183, 2207–2213CrossRefGoogle Scholar
  23. 23.
    Hattne, J., Echols, N., Tran, R., Kern, J., Gildea, R. J., Brewster, A. S., Alonso-Mori, R., Glö ckner, C., Hellmich, J., Laksmono, H., et al. (2014) Accurate macromolecular structures using minimal measurements from X-ray free-electron lasers. Nat. Methods, 11, 545–548CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Kirian, R. A., Wang, X., Weierstall, U., Schmidt, K. E., Spence, J. C. H., Hunter, M., Fromme, P., White, T., Chapman, H. N. and Holton, J. (2010) Femtosecond protein nanocrystallography-data analysis methods. Opt. Express, 18, 5713–5723CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    White, T. A., Kirian, R. A., Martin, A. V., Aquila, A., Nass, K., Barty, A. and Chapman, H. N. (2012) CrystFEL: a software suite for snapshot serial crystallography. J. Appl. Cryst., 45, 335–341CrossRefGoogle Scholar
  26. 26.
    White, T. A. (2014) Post-refinement method for snapshot serial crystallography. Philos. Trans. R. Soc. Lond. B Biol. Sci., 369, 20130330CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Sauter, N. K. (2015) XFEL diffraction: developing processing methods to optimize data quality. J. Synchrotron Radiat., 22, 239–248CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Rossmann, M. G., Leslie, A. G.W., Abdel-Meguid, S. S. and Tsukihara, T. (1979) Processing and post-refinement of oscillation camera data. J. Appl. Cryst., 12, 570–581.CrossRefGoogle Scholar
  29. 29.
    Ginn, H. M., Brewster, A. S., Hattne, J., Evans, G., Wagner, A., Grimes, J. M., Sauter, N. K., Sutton, G. and Stuart, D. I. (2015) A revised partiality model and post-refinement algorithm for X-ray free-electron laser data. Acta Crystallogr. D Biol. Crystallogr., 71, 1400–1410CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Uervirojnangkoorn, M., Zeldin, O. B., Lyubimov, A. Y., Hattne, J., Brewster, A. S., Sauter, N. K., Brunger, A. T. and Weis, W. I. (2015) Enabling X-ray free electron laser crystallography for challenging biological systems from a limited number of crystals. eLife, 4, e05421CrossRefGoogle Scholar
  31. 31.
    Zhang, T., Li, Y. and Wu, L. (2014) An alternative method for data analysis in serial femtosecond crystallography. Acta Crystallogr. A Found. Adv., 70, 670–676CrossRefGoogle Scholar
  32. 32.
    Li, C., Schmidt, K. and Spence, J. C. (2015) Data collection strategies for time-resolved X-ray free-electron laser diffraction, and 2-color methods. Struct. Dyn., 2, 041714CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Loh, N. D., Starodub, D., Lomb, L., Hampton, C. Y., Martin, A. V., Sierra, R. G., Barty, A., Aquila, A., Schulz, J., Steinbrener, J., et al. (2013) Sensing the wavefront of x-ray free-electron lasers using aerosol spheres. Opt. Express, 21, 12385–12394CrossRefPubMedGoogle Scholar
  34. 34.
    Yefanov, O., Gati, C., Bourenkov, G., Kirian, R. A., White, T. A., Spence, J. C. H., Chapman, H. N. and Barty, A. (2014) Mapping the continuous reciprocal space intensity distribution of X-ray serial crystallography. Philos. Trans. R. Soc. Lond. B Biol. Sci., 369, 20130333CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Brehm, W. and Diederichs, K. (2014) Breaking the indexing ambiguity in serial crystallography. Acta Crystallogr. D Biol. Crystallogr., 70, 101–109CrossRefPubMedGoogle Scholar
  36. 36.
    Liu, H., & Spence, J. C. H. (2014) The indexing ambiguity in serial femtosecond crystallography (SFX) resolved using an expectation maximization algorithm. IUCrJ, 1, 393–401CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Barends, T. R. M., Foucar, L., Botha, S., Doak, R. B., Shoeman, R. L., Nass, K., Koglin, J. E., Williams, G. J., Boutet, S., Messerschmidt, M., et al. (2014) De novo protein crystal structure determination from X-ray free-electron laser data. Nature, 505, 244–247CrossRefPubMedGoogle Scholar
  38. 38.
    Spence, J. C. H., Kirian, R. A., Wang, X., Weierstall, U., Schmidt, K. E., White, T., Barty, A., Chapman, H. N., Marchesini, S. and Holton, J. (2011) Phasing of coherent femtosecond X-ray diffraction from sizevarying nanocrystals. Opt. Express, 19, 2866–2873CrossRefPubMedGoogle Scholar
  39. 39.
    Sayre, D. (1952) Some implications of a theorem due to Shannon. Acta Crystallogr., 5, 843CrossRefGoogle Scholar
  40. 40.
    Fienup, J. R. (1982) Phase retrieval algorithms: a comparison. Appl. Opt., 21, 2758–2769CrossRefPubMedGoogle Scholar
  41. 41.
    Kirian, R. A., Bean, R. J., Beyerlein, K. R., Barthelmess, M., Yoon, C. H., Wang, F., Capotondi, F., Pedersoli, E., Barty, A. and Chapman, H. N. (2015) Direct phasing of finite crystals illuminated with a freeelectron laser. Phys. Rev. X, 5, 011015Google Scholar
  42. 42.
    Chen, J. P. J., Spence, J. C. H. and Millane, R. P. (2014) Direct phasing in femtosecond nanocrystallography. I. Diffraction characteristics. Acta Crystallogr. A Found. Adv., 70, 143–153CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Chen, J. P. J., Spence, J. C. H. and Millane, R. P. (2014) Direct phasing in femtosecond nanocrystallography. II. Phase retrieval. Acta Crystallogr. A Found. Adv., 70, 154–161CrossRefPubMedGoogle Scholar
  44. 44.
    Elser, V. (2013) Direct phasing of nanocrystal diffraction. Acta Crystallogr. A, 69, 559–569CrossRefPubMedGoogle Scholar
  45. 45.
    Liu, H., Zatsepin, N. A. and Spence, J. C. H. (2014) Ab-initio phasing using nanocrystal shape transforms with incomplete unit cells. IUCrJ, 1, 19–27CrossRefPubMedGoogle Scholar
  46. 46.
    Ayyer, K., Yefanov, O., Oberthür, D., Roy-Chowdhury, S., Galli, L., Mariani, V., Basu, S., Coe, J., Conrad, C., Fromme, R. (2015) Macromolecular imaging using scattering from disordered crystals. Nature, 530, 202–206CrossRefGoogle Scholar
  47. 47.
    Ekeberg, T., Svenda, M., Abergel, C., Maia, F. R. N. C., Seltzer, V., Claverie, J. -M., Hantke, M., Jö nsson, O., Nettelblad, C., van der Schot, G., et al. (2015) Three-dimensional reconstruction of the giant mimivirus particle with an x-ray free-electron laser. Phys. Rev. Lett., 114, 098102CrossRefPubMedGoogle Scholar
  48. 48.
    Aquila, A., Barty, A., Bostedt, C., Boutet, S., Carini, G., dePonte, D., Drell, P., Doniach, S., Downing, K. H., Earnest, T., et al. (2015) The linac coherent light source single particle imaging road map. Struct. Dyn., 2, 041701CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Deponte, D. P., McKeown, J. T., Weierstall, U., Doak, R. B. and Spence, J. C. H. (2011) Towards ETEM serial crystallography: Electron diffraction from liquid jets. Ultramicroscopy, 111, 824–827CrossRefPubMedGoogle Scholar
  50. 50.
    Bortel, G. and Tegze, M. (2011) Common arc method for diffraction pattern orientation. Acta Crystallogr. A, 67, 533–543CrossRefPubMedGoogle Scholar
  51. 51.
    Kassemeyer, S., Jafarpour, A., Lomb, L., Steinbrener, J., Martin, A. V. and Schlichting, I. (2013) Optimal mapping of x-ray laser diffraction patterns into three dimensions using routing algorithms. Phys. Rev. E Stat. Nonlin. Soft Matter Phys., 88, 042710CrossRefPubMedGoogle Scholar
  52. 52.
    Scheres, S. H. W. (2012) RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol., 180, 519–530CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Loh, N.-T. D. and Elser, V. (2009) Reconstruction algorithm for singleparticle diffraction imaging experiments. Phys. Rev. E Stat. Nonlin. Soft Matter Phys., 80, 026705CrossRefPubMedGoogle Scholar
  54. 54.
    Fung, R., Shneerson, V., Saldin, D. K. and Ourmazd, A. (2009) Structure from fleeting illumination of faint spinning objects in flight. Nat. Phys., 5, 64–67CrossRefGoogle Scholar
  55. 55.
    Dashti, A., Schwander, P., Langlois, R., Fung, R., Li, W., Hosseinizadeh, A., Liaob, H., Pallesenc, J., Sharmab, G., Stupinad, V. et al. (2014) Trajectories of the ribosome as a Brownian nanomachine. Proc. Natl. Acad. Sci. USA, 111, 17492–7CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Takahashi, Y., Suzuki, A., Zettsu, N., Oroguchi, T., Takayama, Y., Sekiguchi, Y., Kobayashi, A., Yamamoto, M. and Nakasako, M. (2013) Coherent diffraction imaging analysis of shape-controlled nanoparticles with focused hard X-ray free-electron laser pulses. Nano Lett., 13, 6028–6032CrossRefPubMedGoogle Scholar
  57. 57.
    Kirian, R. A. (2012) Structure determination through correlated fluctuations in x-ray scattering. J. Phys. At. Mol. Opt. Phys., 45, 223001CrossRefGoogle Scholar
  58. 58.
    Elser, V. (2011) Strategies for processing diffraction data from randomly oriented particles. Ultramicroscopy, 111, 788–792CrossRefPubMedGoogle Scholar
  59. 59.
    Starodub, D., Aquila, A., Bajt, S., Barthelmess, M., Barty, A., Bostedt, C., Bozek, J. D., Coppola, N., Doak, R. B., Epp, S. W., et al. (2012) Single-particle structure determination by correlations of snapshot Xray diffraction patterns. Nat. Commun., 3, 1276CrossRefPubMedGoogle Scholar
  60. 60.
    Poon, H.-C., Schwander, P., Uddin, M. and Saldin, D. K. (2013) Fiber diffraction without fibers. Phys. Rev. Lett., 110, 265505CrossRefPubMedGoogle Scholar
  61. 61.
    Saldin, D. K., Shneerson, V. L., Howells, M. R., Marchesini, S., Chapman, H. N., Bogan, M., Shapiro, D., Kirian, R. A., Weierstall, U., Schmidt, K. E., et al. (2010) Structure of a single particle from scattering by many particles randomly oriented about an axis: toward structure solution without crystallization? New J. Phys., 12, 035014CrossRefGoogle Scholar
  62. 62.
    Kirian, R. A., Schmidt, K. E., Wang, X., Doak, R. B. and Spence, J. C. H. (2011) Signal, noise, and resolution in correlated fluctuations from snapshot small-angle x-ray scattering. Phys. Rev. E Stat. Nonlin. Soft Matter Phys., 84, 011921CrossRefPubMedGoogle Scholar
  63. 63.
    Kodama, W. and Nakasako, M. (2011) Application of a real-space three-dimensional image reconstruction method in the structural analysis of noncrystalline biological macromolecules enveloped by water in coherent x-ray diffraction microscopy. Phys. Rev. E Stat. Nonlin. Soft Matter Phys., 84, 021902CrossRefPubMedGoogle Scholar
  64. 64.
    Tenboer, J., Basu, S., Zatsepin, N., Pande, K., Milathianaki, D., Frank, M., Hunter, M., Boutet, S., Williams, G. J., Koglin, J. E., et al. (2014) Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein. Science, 346, 1242–1246CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Arnlund, D., Johansson, L. C., Wickstrand, C., Barty, A., Williams, G. J., Malmerberg, E., Davidsson, J., Milathianaki, D., DePonte, D. P., Shoeman, R. L., et al. (2014) Visualizing a protein quake with timeresolved X-ray scattering at a free-electron laser. Nat. Methods, 11, 923–926CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Alber, F., Dokudovskaya, S., Veenhoff, L. M., Zhang, W., Kipper, J., Devos, D., Suprapto, A., Karni-Schmidt, O., Williams, R., Chait, B. T., et al. (2007) The molecular architecture of the nuclear pore complex. Nature, 450, 695–701CrossRefPubMedGoogle Scholar
  67. 67.
    Vartanyants, I. A., Robinson, I. K., McNulty, I., David, C., Wochner, P. and Tschentscher, T. (2007) Coherent X-ray scattering and lensless imaging at the European XFEL Facility. J. Synchrotron Radiat., 14, 453–470CrossRefPubMedGoogle Scholar
  68. 68.
    Maia, F. R. N. C. (2012) The Coherent X-ray Imaging Data Bank. Nat. Methods, 9, 854–855CrossRefPubMedGoogle Scholar
  69. 69.
    Kern, J., Alonso-Mori, R., Tran, R., Hattne, J., Gildea, R. J., Echols, N., Glöckner, C., Hellmich, J., Laksmono, H., Sierra, R. G., et al. (2013) Simultaneous femtosecond X-ray spectroscopy and diffraction of photosystem II at room temperature. Science, 340, 491–495CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH 2016

Authors and Affiliations

  1. 1.Complex Systems DivisionBeijing Computational Science Research CenterBeijingChina
  2. 2.Physics DepartmentArizona State UniversityTempeUSA

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