Amino Acids

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Globular protein backbone conformational disorder in crystal structures

  • Oliviero CarugoEmail author
Original Article


Proteins are not static molecules but dynamic entities able to modify their structure for several reasons, from the necessity to recognize partners to the regulation of their thermodynamic stability. Conformational disorder is frequent in protein structures and atoms can have, in protein crystal structures, two or more alternative, equilibrium positions close to each other. Here, a set of protein crystal structures refined at very high resolution (1 Å or better) is examined to characterize the conformational disorder of the backbone atoms, which is not infrequent: about 15% of the protein backbone atoms are conformationally disordered and three quarters of them have been deposited with two or more equilibrium positions (most of the others were not detected in the electron density maps). Several structural features have been examined and it was observed that Cα atoms tend to be disordered more frequently than the other backbone atoms, likely because their disorder is induced by disordered side chains: side-chain disorder is two times more frequent than backbone disorder. Surprisingly, backbone disorder is only slightly more frequent in loops than in helices and strands and this is in agreement with the observation that backbone disorder is a localized phenomenon: in about 80% of the cases, it is observed in one amino acid and not in its neighbors. However, although backbone disorder does not cluster along the polypeptide sequence, it tends to cluster in 3D, since backbone-disordered amino acids distant in sequence are close in the 3D space.


Conformational disorder Protein backbone Protein crystal structure 



Kristina Djinovic is gratefully acknowledged for her kind hospitality at the University of Vienna and for helpful discussions.


This work was supported by the MIUR-FFABR and by the University of Pavia.

Compliance with ethical statement

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

726_2018_2683_MOESM1_ESM.docx (455 kb)
Supplementary material 1 (DOCX 455 kb)


  1. Atkins P, de Paula J (2014) Physical chemistry: thermodynamics, structure and change. W. H. Freeman, OxfordGoogle Scholar
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bernstein FC, Koetzle TF, Williams GJB, Meyer EFJ, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M (1977) The protein data bank: a computer-based archival file for macromolecular structures. J Mol Biol 112:535–542CrossRefPubMedGoogle Scholar
  4. Bowler BE (2012) Residual structure in unfolded proteins. Curr Opin Struct Biol 22:4–13CrossRefPubMedGoogle Scholar
  5. Carugo O (2018a) How large B-factors can be in protein crystal structures. BMC Bioinform 19:61CrossRefGoogle Scholar
  6. Carugo O (2018b) Atomic displacement parameters in structural biology. Amino Acids 50:775–786CrossRefGoogle Scholar
  7. Carugo O (2018c) Maximal B-factors in protein crystal structures. Zeit Krist. CrossRefGoogle Scholar
  8. Carugo O, Djinović-Carugo K (2012) How many packing contacts are observed in protein crystals? J Struct Biol 180:96–100CrossRefPubMedGoogle Scholar
  9. Chou PY, Fasman GD (1974) Prediction of protein conformation. Biochemistry 13:222–245CrossRefPubMedGoogle Scholar
  10. Dauter Z, Lamzin VS, Wilson KS (1997) The benefits of atomic resolution. Curr Opin Struct Biol 7:681–688CrossRefPubMedGoogle Scholar
  11. Djinovic Carugo K, Carugo O (2015) Missing strings of residues in protein crystal structures. Intrinsically Disord Proteins 3:1–7CrossRefGoogle Scholar
  12. Frauenfelder H, Chen G, Berendzen J, Fenimore PW, Jansson H, McMahon BH, Stroe IR, Swenson J, Young RD (2009) A unified model of protein dynamics. Proc Natl Acad Sci USA 106:5129–5134CrossRefPubMedGoogle Scholar
  13. Hintze BJ, Lewis SM, Richardson JS, Richardson DC (2016) Molprobity’s ultimate rotamer-library distributions for model validation. Proteins 84:1177–1189CrossRefPubMedPubMedCentralGoogle Scholar
  14. Hubbard SJ, Thornton JM (1993) NACCESS. Department of Biochemistry and Molecular Biology, University College, LondonGoogle Scholar
  15. Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22:2577–2637CrossRefPubMedGoogle Scholar
  16. Lesk AM (2016) Introduction to protein science, 3rd edn. Oxford University Press, OxfordGoogle Scholar
  17. Lovell SC, Word JM, Richardson JS, Richardson DC (2000) The penultimate rotamer library. Proteins 40:389–408CrossRefPubMedGoogle Scholar
  18. Piovesan D, Tabaro F, Mičetić I, Necci M, Quaglia F, Oldfield CJ, Aspromonte MC, Davey NE, Davidović R, Dosztányi Z, Elofsson A, Gasparini A, Hatos A, Kajava AV, Kalmar L, Leonardi E, Lazar T, Macedo-Ribeiro S, Macossay-Castillo M, Meszaros A, Minervini G, Murvai N, Pujols J, Roche DB, Salladini E, Schad E, Schramm A, Szabo B, Tantos A, Tonello F, Tsirigos KD, Veljković N, Ventura S, Vranken W, Warholm P, Uversky VN, Dunker AK, Longhi S, Tompa P, Tosatto SC (2017) DisProt 7.0: a major update of the database of disordered proteins. Nucleic Acids Res 45:D1123–D1124CrossRefPubMedGoogle Scholar
  19. Schrauber H, Eisenhaber F, Argos P (1993) Rotamers: to be or not to be? An analysis of amino acid side-chain conformations in globular proteins. J Mol Biol 230:592–612CrossRefPubMedGoogle Scholar
  20. Tompa P (2010) Structure and function of intrinsically disordered proteins. Chapman & Hall, Boca RatonGoogle Scholar
  21. Viterbo D (2002) Solution and refinement of crystal structures. In: Giacovazzo C (ed) Fundamentals of crystallography. Oxford University Press, New York, pp 413–501Google Scholar
  22. Vitkup D, Ringe D, Petsko GA, Karplus M (2000) Solvent mobility and the protein ‘glass’ transition. Nat Struct Biol 7:34–38CrossRefPubMedGoogle Scholar
  23. Wong KB, Daggett V (1998) Barstar has a highly dynamic hydrophobic core: evidence from molecular dynamics simulations and nuclear magnetic resonance relaxation data. Biochemistry 37:11182–11192CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of PaviaPaviaItaly
  2. 2.Department of Structural and Computational BiologyUniversity of ViennaViennaAustria

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