Skip to main content
SpringerLink
Log in

Structure Determination Software for Macromolecular X-Ray Crystallography

  • Protocol
  • First Online:
Advanced Methods in Structural Biology

Part of the book series: Springer Protocols Handbooks ((SPH))

  • 1445 Accesses

Abstract

Because of the phase problem in crystallography, electron density maps can only be calculated based on the substructure of heavy atoms (experimental phasing) or known homology structure (molecular replacement) to determine the macromolecular structure. Such phasing methods include various errors and are limited by the observed diffraction resolution of crystals. Therefore, various mathematic methods and excellent software packages have been developed for structure determination. Specially, structural genomics projects have advanced the development of powerful and automated methods for macromolecular crystallography during the past decade. In this chapter, typical software often used for structure determination will be introduced. We begin with an overview of the structure determination process and simple mathematic methods in each section. After introducing software packages used in each step, we will mention the strategy/practice for each process of structure determination.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Official Nobel Prize site http://www.nobelprize.org/nobel_prizes/physics/laureates/1914/

  2. Bragg WH (1912) X-rays and crystals. Nature 90:360–361

    Article  Google Scholar 

  3. Bragg WL (1912) The specular reflection of x-rays. Nature 90:410–410

    Article  Google Scholar 

  4. Official Nobel Prize site http://www.nobelprize.org/nobel_prizes/physics/laureates/1915/

  5. Bernal JD, Crowfoot D (1934) X-ray photographs of crystalline pepsin. Nature 133:794–795

    Article  CAS  Google Scholar 

  6. Kendrew JC, Dickerson RE, Strandberg BE, Hart RG, Dvies DR (1960) Structure of myoglobin: a three-dimensional fourier synthesis at 2 Å resolution. Nature 185:422–427

    Article  CAS  PubMed  Google Scholar 

  7. Perutz MF, Rossmann MG, Cullis ANNF, Muirhead H, Will G, North ACT (1960) Structure of hæmoglobin: a three-dimensional fourier synthesis at 5.5-Å. Resolution obtained by X-ray analysis. Nature 185:416–422

    Article  CAS  PubMed  Google Scholar 

  8. Collaborative Computational Project, Number 4 (1994) The CCP4 suite: programs for protein crystallography. Acta Crystallogr D50:760–763

    Google Scholar 

  9. Yao M, Zhou Y, Tanaka I (2006) LAFIRE: software for automating the refinement process of protein-structure analysis. Acta Crystallogr D62:189–196

    CAS  Google Scholar 

  10. Yamashita K, Zhou Y, Tanaka I, Yao M (2013) New model-fitting and model-completion programs for automated iterative nucleic acid refinement. Acta Crystallogr D69:1171–1179

    Google Scholar 

  11. Potterton E, Briggs P, Turkenburg M, Dodson E (2003) A graphical user interface to the CCP4 program suite. Acta Crystallogr D59:1131–1137

    CAS  Google Scholar 

  12. Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P, Evans PR, Keegan RM, Krissinel EB, Leslie AGW, McCoy A, McNicholas SJ, Murshudov GN, Pannu NS, Potterton EA, Powell HR, Read RJ, Vagin A, Wilson KS (2011) Overview of the CCP4 suite and current developments. Acta Crystallogr D67:235–242

    Google Scholar 

  13. Minor W, Cymborowski M, Otwinowskib Z, Chruszcz M (2006) HKL-3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes. Acta Crystallogr D59:45–49

    Google Scholar 

  14. Adams PD, Grosse-Kunstleve RW, Hung LW, Ioerger TR, McCoy AJ, Moriarty NW, Read RJ, Sacchettini JC, Sauter NK, Terwilliger TC (2002) PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr D58:1948–1956

    CAS  Google Scholar 

  15. Adams PD, Afonine PV, Bunkóczi G, Chen VB, Davis IW, Echols N, Headd JJ, Hung LW, Kapral GJ, Grosse-Kunstleve RW, McCoy AJ, Moriarty NW, Oeffner R, Read RJ, Richardson DC, Richardson JS, Terwilliger TC, Zwart PH (2010) PHENIX: a comprehensive python-based system for macromolecular structure solution. Acta Crystallogr D66:213–221

    Google Scholar 

  16. Emsley P, Cowtan K (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D60:2126–2132

    CAS  Google Scholar 

  17. Kabsch W (2010) XDS. Acta Crystallogr D66:125–132

    Google Scholar 

  18. Otwinowski Z, Minor W (1997) Processing of x-ray diffraction data collection in oscillation mode. Methods Enzymol 276:307–326

    Article  CAS  Google Scholar 

  19. Leslie AGW (1993) Auto-indexing of rotating diffraction images and parameter refinement. In: Sawyer L, Isaacs N, Bailey S (eds) Proceeding of the CCP4 study weekend. Daresbury Laboratory, Daresbury, pp 44–51

    Google Scholar 

  20. Evans PR (1997) Scaling of MAD data. In: Wilson KS, Davies G, Ashton AW, Bailey S (eds) Proceedings of CCP4 study weekend. Daresbury Laboratory, Daresbury, pp 97–102

    Google Scholar 

  21. Battye TGG, Kontogiannis L, Johnson O, Powell HR, Leslie AGW (2011) iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM. Acta Crystallogr D67:271–281

    Google Scholar 

  22. Yamashita K, Kawai Y, Tanaka Y, Hirano N, Kaneko J, Tomita N, Ohta M, Kamio Y, Yao M, Tanaka I (2011) Crystal structure of the octameric pore of staphylococcal γ-hemolysin reveals the β-barrel pore formation mechanism by two components. Proc Natl Acad Sci U S A 108:17314–17319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Brunger AT (1997) Patterson correlation searches and refinement. Methods Enzymol 276:558–580

    Google Scholar 

  24. Navaza J (1994) AmoRe: an automated package for molecular replacement. Acta Crystallogr A50:157–163

    Article  CAS  Google Scholar 

  25. Vagin A, Teplyakov A (1997) MOLREP: an automated program for molecular replacement. J Appl Cryst 30:1022–1025

    Article  CAS  Google Scholar 

  26. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ (2007) Phaser crystallographic software. J Appl Cryst 40:658–674

    Article  CAS  Google Scholar 

  27. Bunkoczi G, Read JRJ (2011) Improvement of molecular-replacement models with Sculptor. Acta Crystallogr D67:303–312

    Google Scholar 

  28. Zheng A, Yu J, Yamamoto R, Ose T, Tanaka I, Yao M (2014) X-ray structures of eIF5B and eIF5B-eIF1A complex: conformational flexibility of eIF5B restricted on the ribosome by interaction with eIF1A. Acta Crystallogr D70:3090–3098

    Google Scholar 

  29. Kelley LA, Sternberg MJE (2009) Protein structure prediction on the web: a case study using the phyre server. Nat Protoc 4:363–371

    Article  CAS  PubMed  Google Scholar 

  30. Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Kiefer F, Cassarino TG, Bertoni M, Bordoli L, Schwede T (2014) SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res V12:W252–W258

    Article  Google Scholar 

  31. Rohl CA, Strauss CEM, Misura KMS, Baker D (2004) Protein structure prediction using Rosetta. Methods Enzymol 383:66–93

    Article  CAS  PubMed  Google Scholar 

  32. Fujiwara T, Saburi W, Inoue S, Mori H, Matsui H, Tanaka I, Yao M (2013) Crystal structure of Ruminococcus albus cellobiose 2-epimerase: structural insights into epimerization of unmodified sugar. FEBS Lett 587:840–846

    Article  CAS  PubMed  Google Scholar 

  33. Sheldrick GM (2008) A short history of SHELX. Acta Crystallogr A64:112–122

    Article  Google Scholar 

  34. Schneider TR, Sheldrick GM (2002) Substructure solution with SHELXD. Acta Crystallogr D58:1772–1779

    CAS  Google Scholar 

  35. Sheldrick GM (2010) Experimental phasing with SHELXC/D/E: combining chain tracing with density modification. Acta Crystallogr D66:479–485

    Google Scholar 

  36. Yasutake Y, Watanabe S, Yao M, Takada Y, Fukunaga N, Tanaka I (2003) Crystal structure of the monomeric isocitrate dehydrogenase in the presence of NADP+: insight into the cofactor recognition, catalysis, and evolution. J Biol Chem 278:36897–36904

    Article  CAS  PubMed  Google Scholar 

  37. de La Fortelle E, Bricogne G (1997) Maximum-likelihood heavy-atom parameter refinement for multiple isomorphous replacement and multiwavelength anomalous diffraction methods. Methods Enzymol 276:472–494

    Article  Google Scholar 

  38. Terwilliger TC, Adams PD, Read RJ, McCoy AJ, Moriarty NW, Grosse-Kunstleve RW, Afonine PV, Zwart PH, Hung LW (2009) Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard. Acta Crystallogr D65:582–601

    Google Scholar 

  39. Abrahams JP, Leslie AGW (1996) Methods used in the structure determination of bovine mitochondrial F1 ATPase. Acta Crystallogr D52:30–42

    CAS  Google Scholar 

  40. Morris RJ, Perrakis A, Lamzin VS (2003) ARP/wARP and automatic interpretation of protein electron density maps. Method Enzymol (Carter C, Sweet B (eds)) 374:229–244

    Google Scholar 

  41. Sheldrich GM, Schneider TR (1997) SHELXL: high-resolution refinement. Methods Enzymol 277:319–343

    Article  Google Scholar 

  42. Tronrud DE, Ten Eyck LF, Matthews BW (1987) An efficient general-purpose least-squares refinement program for macromolecular structures. Acta Crystallogr A43:489–501, http://www.globalphasing.com/buster/

    Article  CAS  Google Scholar 

  43. Bricogne G, Irwin J (1996) Proceedings of the CCP4 study weekend. In: Dodson E, Moore M, Ralph A, Bailey S (eds) Macromolecular refinement. Daresbury Laboratory, Warrington, pp 85–92

    Google Scholar 

  44. Brünger AT, Kuriyan J, Karplus M (1987) Crystallographic R factor refinement by molecular dynamics. Science 235:458–460

    Article  PubMed  Google Scholar 

  45. Brünger AT, Adams PD, Clore GM, DeLano WL, Gros P, Grosse-Kunstleve RW, Jiang JS, Kuszewski J, Nilges M, Pannu NS, Read RJ, Rice LM, Simonson T, Warren GL (1998) Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr D54:905–921

    Google Scholar 

  46. Murshudov GN, Vagin AA, Dodson EJ (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D53:240–255

    CAS  Google Scholar 

  47. Afonine PV, Grosse-Kunstleve RW, Echols N, Headd JJ, Moriarty NW, Mustyakimov M, Terwilliger TC, Urzhumtsev A, Zwart PH, Adams PD (2012) Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr D68:352–367

    Google Scholar 

  48. Engh RA, Huber R (1991) Accurate bond and angle parameters for X-ray protein structure refinement. Acta Crystallogr A47:392–400

    Article  CAS  Google Scholar 

  49. Jack A, Levitt M (1978) Refinement of large structures by simultaneous minimization of energy and R factor. Acta Crystallogr A34:931–935

    Article  CAS  Google Scholar 

  50. Brünger AT (1992) Refinement of large structures by simultaneous minimization of energy and R factor. Nature 355:472–475

    Article  PubMed  Google Scholar 

  51. Nakamuraa A, Nemoto T, Heinemann IU, Yamashita K, Sonoda T, Komoda K, Tanaka I, Söll D, Yao M (2013) Structural basis of reverse nucleotide polymerization. Proc Natl Acad Sci U S A 110:20970–20975

    Article  Google Scholar 

  52. Liu YC, Nakamura A, Nakazawa Y, Asano N, Ford KA, Hohn MJ, Tanaka I, Yao M, Söll D (2014) Ancient translation factor is essential for tRNA-dependent cysteine biosynthesis in methanogenic archaea. Proc Natl Acad Sci U S A 111:10520–10525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kostrewa D (1997) Bulk solvent correction: practical application and effects in reciprocal and real space. CCP4 Newsl. Protein Crystallogr 34:9–22

    Google Scholar 

  54. Schomaker V, Trueblood KN (1968) On the rigid-body motion of molecules in crystals. Acta Crystallogr B24:63–76

    Article  Google Scholar 

  55. Winn M, Isupov M, Murshudov GN (2001) Use of TLS parameters to model anisotropic displacements in macromolecular refinement. Acta Crystallogr D57:122–133

    CAS  Google Scholar 

Download references

Acknowledgments

We thank Professor Isao Tanaka for helpful advices and provision of some figures, Drs. Yong Zhou and Yamashita for developing program LAFIRE, and all members of X-ray structure biology laboratory, Faculty of Advanced Life Science, Hokkaido University, JAPAN for providing the information of structure determinations. This work was partly supported by Grants-in-Aid for Scientific Research in a Priority Area and the National Project on Protein Structural and Functional Analysis, from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Author information

Authors and Affiliations

  1. Faculty of Advanced Life Science, Hokkaido University, Kita-10, Nishi-8, Kita-Ku, Sapporo, 060-0810, Japan

    Min Yao

Authors
  1. Min Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Min Yao .

Editor information

Editors and Affiliations

  1. Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK) , Tsukuba, Ibaraki, Japan

    Toshiya Senda

  2. Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan

    Katsumi Maenaka

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Japan

About this protocol

Cite this protocol

Yao, M. (2016). Structure Determination Software for Macromolecular X-Ray Crystallography. In: Senda, T., Maenaka, K. (eds) Advanced Methods in Structural Biology. Springer Protocols Handbooks. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56030-2_16

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-56030-2_16

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-56028-9

  • Online ISBN: 978-4-431-56030-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation