Integrative/Hybrid Methods Structural Biology: Role of Macromolecular Crystallography

  • Stephen K. BurleyEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1105)


Macromolecular crystallography has been central to the emergence and development of structural biology as a scientific discipline. Approximately 90% of the more than 138,000 three-dimensional structures currently available in the Protein Data Bank (PDB) archive, the single, global open access data resource for macromolecular structure data, were determined using X-ray crystallography. MX, the enormous variety of PDB structures of proteins, DNA, and RNA, and computational models derived therefrom will be central to the growth of integrative or hybrid (I/H) methods structural studies of macromolecular assemblies and other complex biological systems.


X-ray crystallography Macromolecular crystallography MX Protein crystallography 3D structure Protein DNA RNA Protein data Bank PDB Worldwide protein data Bank wwPDB Atomic coordinates Structural biology Integrative/hybrid methods I/H methods 



The RCSB PDB is jointly funded by the National Science Foundation, the National Institutes of Health, and the Department of Energy (NSF-DBI 1338415). We gratefully acknowledge help from Brian Hudson with figure preparation, and Nicole Oorbeek with manuscript preparation, and contributions from all members of the Research Collaboratory for Structural Bioinformatics Protein Data Bank and our Worldwide Protein Data Bank partners.


  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The Protein Data Bank. Nucleic Acids Res 28(1):235–242. CrossRefPubMedPubMedCentralGoogle Scholar
  2. Berman HM, Henrick K, Nakamura H (2003) Announcing the worldwide protein data Bank. Nat Struct Biol 10(12):980. CrossRefPubMedGoogle Scholar
  3. Brunger AT, DeLaBarre B, Davies JM, Weis WI (2009) X-ray structure determination at low resolution. Acta Crystallogr Ser D 65(Pt 2):128–133. CrossRefGoogle Scholar
  4. Burley SK, Kurisu G, Markley JL, Nakamura H, Velankar S, Berman HM, Sali A, Schwede T, Trewhella J (2017) PDB-dev: a prototype system for depositing integrative/hybrid structural models. Structure 25:1317–1318CrossRefGoogle Scholar
  5. DiMaio F, Echols N, Headd JJ, Terwilliger TC, Adams PD, Baker D (2013) Improved low-resolution crystallographic refinement with Phenix and Rosetta. Nat Methods 10(11):1102–1104. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Dyda F (2010) Developments in low-resolution biological X-ray crystallography. F1000 Biol Rep 2:80.
  7. Fitzgerald PMD, Westbrook JD, Bourne PE, McMahon B, Watenpaugh KD, Berman HM (2005) 4.5 macromolecular dictionary (mmCIF). In: Hall SR, McMahon B (eds) International tables for crystallography G. Definition and exchange of crystallographic data. Springer, Dordrecht, pp 295–443Google Scholar
  8. Goh BC, Hadden JA, Bernardi RC, Singharoy A, McGreevy R, Rudack T, Cassidy CK, Schulten K (2016) Computational methodologies for real-space structural refinement of large macromolecular complexes. Annu Rev Biophys 45:253–278. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Gore S, Sanz Garcia E, Hendrickx PMS, Gutmanas A, Westbrook JD, Yang H, Feng Z, Baskaran K, Berrisford JM, Hudson BP, Ikegawa Y, Kobayashi N, Lawson CL, Mading S, Mak L, Mukhopadhyay A, Oldfield TJ, Patwardhan A, Peisach E, Sahni G, Sekharan MR, Sen S, Shao C, Smart OS, Ulrich EL, Yamashita R, Quesada M, Young JY, Nakamura H, Markley JL, Berman HM, Burley SK, Velankar S, Kleywegt GJ (2017) Validation of the structures in the protein data bank. Structure 25:1916–1927. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Karmali AM, Blundell TL, Furnham N (2009) Model-building strategies for low-resolution X-ray crystallographic data. Acta Crystallogr Ser D 65(Pt 2):121–127. CrossRefGoogle Scholar
  11. Kinjo AR, Bekker GJ, Suzuki H, Tsuchiya Y, Kawabata T, Ikegawa Y, Nakamura H (2017) Protein data bank Japan (PDBj): updated user interfaces, resource description framework, analysis tools for large structures. Nucleic Acids Res 45(D1):D282–D288. CrossRefPubMedGoogle Scholar
  12. Phillips GN Jr (1986) Construction of an atomic model for tropomyosin and implications for interactions with actin. J Mol Biol 192(1):128–131CrossRefGoogle Scholar
  13. Protein Data Bank (1971) Crystallography: protein data bank. Nature New Biol 233(42):223–223. CrossRefGoogle Scholar
  14. Rose PW, Prlic A, Altunkaya A, Bi C, Bradley AR, Christie CH, Costanzo LD, Duarte JM, Dutta S, Feng Z, Green RK, Goodsell DS, Hudson B, Kalro T, Lowe R, Peisach E, Randle C, Rose AS, Shao C, Tao YP, Valasatava Y, Voigt M, Westbrook JD, Woo J, Yang H, Young JY, Zardecki C, Berman HM, Burley SK (2017) The RCSB protein data bank: integrative view of protein, gene and 3D structural information. Nucleic Acids Res 45(D1):D271–D281. CrossRefPubMedGoogle Scholar
  15. Shi Y, Fernandez-Martinez J, Tjioe E, Pellarin R, Kim SJ, Williams R, Schneidman-Duhovny D, Sali A, Rout MP, Chait BT (2014) Structural characterization by cross-linking reveals the detailed architecture of a coatomer-related heptameric module from the nuclear pore complex. Mol Cell Proteomics 13(11):2927–2943. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Ulrich EL, Akutsu H, Doreleijers JF, Harano Y, Ioannidis YE, Lin J, Livny M, Mading S, Maziuk D, Miller Z, Nakatani E, Schulte CF, Tolmie DE, Kent Wenger R, Yao H, Markley JL (2008) BioMagResBank. Nucleic Acids Res 36(Database issue):D402–D408. CrossRefPubMedGoogle Scholar
  17. Velankar S, van Ginkel G, Alhroub Y, Battle GM, Berrisford JM, Conroy MJ, Dana JM, Gore SP, Gutmanas A, Haslam P, Hendrickx PM, Lagerstedt I, Mir S, Fernandez Montecelo MA, Mukhopadhyay A, Oldfield TJ, Patwardhan A, Sanz-Garcia E, Sen S, Slowley RA, Wainwright ME, Deshpande MS, Iudin A, Sahni G, Salavert Torres J, Hirshberg M, Mak L, Nadzirin N, Armstrong DR, Clark AR, Smart OS, Korir PK, Kleywegt GJ (2016) PDBe: improved accessibility of macromolecular structure data from PDB and EMDB. Nucleic Acids Res 44(D1):D385–D395. CrossRefPubMedGoogle Scholar
  18. Webb B, Viswanath S, Bonomi M, Pellarin R, Greenberg CH, Saltzberg D, Sali A (2018) Integrative structure modeling with the integrative modeling platform. Protein Sci 27(1):245–258. CrossRefPubMedGoogle Scholar
  19. Young JY, Westbrook JD, Feng Z, Sala R, Peisach E, Oldfield TJ, Sen S, Gutmanas A, Armstrong DR, Berrisford JM, Chen L, Chen M, Di Costanzo L, Dimitropoulos D, Gao G, Ghosh S, Gore S, Guranovic V, Hendrickx PMS, Hudson BP, Igarashi R, Ikegawa Y, Kobayashi N, Lawson CL, Liang Y, Mading S, Mak L, Mir MS, Mukhopadhyay A, Patwardhan A, Persikova I, Rinaldi L, Sanz-Garcia E, Sekharan MR, Shao C, Swaminathan GJ, Tan L, Ulrich EL, van Ginkel G, Yamashita R, Yang H, Zhuravleva MA, Quesada M, Kleywegt GJ, Berman HM, Markley JL, Nakamura H, Velankar S, Burley SK (2017) OneDep: unified wwPDB system for deposition, biocuration, and validation of macromolecular structures in the PDB archive. Structure 25(3):536–545. CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Rutgers, The State University of New JerseyPiscatawayUSA

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