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Stereochemistry and Validation of Macromolecular Structures

  • Alexander WlodawerEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1607)

Abstract

Macromolecular structure is governed by the strict rules of stereochemistry. Several approaches to the validation of the correctness of the interpretation of crystallographic and NMR data that underlie the models deposited in the PDB are utilized in practice. The stereochemical rules applicable to macromolecular structures are discussed in this chapter. Practical, computer-based methods and tools of verification of how well the models adhere to those established structural principles to assure their quality are summarized.

Key words

Crystal structure NMR structure Ramachandran plot Bond lengths Bond angles Quality check Geometrical criteria Protein Data Bank (PDB) 

References

  1. 1.
    Allen FH (2002) The Cambridge Structural Database: a quarter of a million crystal structures and rising. Acta Crystallogr B 58:380–388CrossRefPubMedGoogle Scholar
  2. 2.
    Sheldrick GM (1990) Phase annealing in SHELX-90: direct methods for larger structures. Acta Crystallogr A 46:467–473CrossRefGoogle Scholar
  3. 3.
    Berman HM, Westbrook J, Feng Z et al (2000) The Protein Data Bank. Nucleic Acids Res 28:235–242CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pauling L, Corey RB, Branson HR (1951) The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain. Proc Natl Acad Sci U S A 37:205–211CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Pauling L, Corey RB (1951) The pleated sheet, a new layer configuration of polypeptide chains. Proc Natl Acad Sci U S A 37:251–256CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Pauling L, Corey RB (1953) Stable configurations of polypeptide chains. Proc R Soc Lond B 141:21–33CrossRefPubMedGoogle Scholar
  7. 7.
    Kendrew JC, Bodo G, Dintzis HM et al (1958) A three-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature 181:662–666CrossRefPubMedGoogle Scholar
  8. 8.
    Perutz MF, Rossmann MG, Cullis AF et al (1960) Structure of haemoglobin: a three-dimensional Fourier synthesis at 5.5-Å resolution, obtained by X-ray analysis. Nature 185:416–421CrossRefPubMedGoogle Scholar
  9. 9.
    Blake CC, Fenn RH, North AC et al (1962) Structure of lysozyme. A Fourier map of the electron density at 6 Å resolution obtained by X-ray diffraction. Nature 196:1173–1176CrossRefPubMedGoogle Scholar
  10. 10.
    Watson JD, Crick FH (1953) Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171:737–738CrossRefPubMedGoogle Scholar
  11. 11.
    Evans PR (2007) An introduction to stereochemical restraints. Acta Crystallogr D Biol Crystallogr 63:58–61CrossRefPubMedGoogle Scholar
  12. 12.
    Wlodawer A, Hendrickson WA (1982) A procedure for joint refinement of macromolecular structures with X-ray and neutron diffraction data from single crystals. Acta Crystallogr A 38:239–247CrossRefGoogle Scholar
  13. 13.
    Hendrickson WA (1985) Stereochemically restrained refinement of macromolecular structures. Methods Enzymol 115:252–270CrossRefPubMedGoogle Scholar
  14. 14.
    Brünger AT, Adams PD, Clore GM et al (1998) Crystallography and NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr 54:905–921CrossRefPubMedGoogle Scholar
  15. 15.
    Sheldrick GM, Schneider TR (1997) SHELXL: high-resolution refinement. Methods Enzymol 277:319–343CrossRefPubMedGoogle Scholar
  16. 16.
    Murshudov GN, Skubak P, Lebedev AA et al (2011) REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr D Biol Crystallogr 67:355–367CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Adams PD, Grosse-Kunstleve RW, Hung LW et al (2002) PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr D Biol Crystallogr 58:1948–1954CrossRefPubMedGoogle Scholar
  18. 18.
    Engh R, Huber R (1991) Accurate bond and angle parameters for X-ray protein-structure refinement. Acta Crystallogr A 47:392–400CrossRefGoogle Scholar
  19. 19.
    Engh RA, Huber R (2001) International tables for crystallography. Kluwer Academic Publishers, Dordrecht, pp 382–392Google Scholar
  20. 20.
    Jaskolski M, Gilski M, Dauter Z, Wlodawer A (2007) Stereochemical restraints revisited: how accurate are refinement targets and how much should protein structures be allowed to deviate from them? Acta Crystallogr D Biol Crystallogr 63:611–620CrossRefPubMedGoogle Scholar
  21. 21.
    Tronrud DE, Karplus PA (2011) A conformation-dependent stereochemical library improves crystallographic refinement even at atomic resolution. Acta Crystallogr D Biol Crystallogr 67:699–706CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Malinska M, Dauter M, Kowiel M et al (2015) Protonation and geometry of histidine rings. Acta Crystallogr D Biol Crystallogr 71:1444–1454CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Parkinson G, Vojtechovsky J, Clowney L et al (1996) New parameters for the refinement of nucleic acid-containing structures. Acta Crystallogr D Biol Crystallogr 52:57–64CrossRefPubMedGoogle Scholar
  24. 24.
    Brzezinski K, Brzuszkiewicz A, Dauter M et al (2011) High regularity of Z-DNA revealed by ultra high-resolution crystal structure at 0.55 Å. Nucleic Acids Res 39:6238–6248CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ramakrishnan C, Ramachandran GN (1965) Stereochemical criteria for polypeptide and protein chain conformations: II. Allowed conformation for a pair of peptide units. Biophys J 5:909–933CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Read RJ, Adams PD, Arendall WB III et al (2011) A new generation of crystallographic validation tools for the protein data bank. Structure 19:1395–1412CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Laskowski RA, MacArthur MW, Moss DS et al (1993) PROCHECK: program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283–291CrossRefGoogle Scholar
  28. 28.
    Kleywegt GJ, Jones TA (1996) Phi/psi-chology: Ramachandran revisited. Structure 4:1395–1400CrossRefPubMedGoogle Scholar
  29. 29.
    Weiss MS, Hilgenfeld R (1997) On the use of the merging R factor as a quality indicator for X-ray data. J Appl Crystallogr 30:203–205CrossRefGoogle Scholar
  30. 30.
    Stewart DE, Sarkar A, Wampler JE (1990) Occurrence and role of cis peptide bonds in protein structures. J Mol Biol 214:253–260CrossRefPubMedGoogle Scholar
  31. 31.
    Touw WG, Joosten RP, Vriend G (2015) Detection of trans-cis flips and peptide-plane flips in protein structures. Acta Crystallogr D Biol Crystallogr 71:1604–1614CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Croll TI (2015) The rate of cis-trans conformation errors is increasing in low-resolution crystal structures. Acta Crystallogr D Biol Crystallogr 71:706–709CrossRefPubMedGoogle Scholar
  33. 33.
    EU 3-D Validation Network (1998) Who checks the checkers? Four validation tools applied to eight atomic resolution structures. J Mol Biol 276:417–436CrossRefGoogle Scholar
  34. 34.
    Addlagatta A, Krzywda S, Czapinska H et al (2001) Ultrahigh-resolution structure of a BPTI mutant. Acta Crystallogr D Biol Crystallogr 57:649–663CrossRefPubMedGoogle Scholar
  35. 35.
    Chellapa GD, Rose GD (2015) On interpretation of protein X-ray structures: planarity of the peptide unit. Proteins 83:1687–1692CrossRefPubMedGoogle Scholar
  36. 36.
    Brereton AE, Karplus PA (2016) On the reliability of peptide nonplanarity seen in ultra-high resolution crystal structures. Protein Sci 25:926–932CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Brändén C-I, Jones TA (1990) Between objectivity and subjectivity. Nature 343:687–689CrossRefGoogle Scholar
  38. 38.
    Jones TA (1985) Interactive computer graphics: FRODO. Methods Enzymol 115:157–171CrossRefPubMedGoogle Scholar
  39. 39.
    Jones TA, Zou JY, Cowan S et al (1991) Improved methods for building protein models in electron density maps and location of errors in these models. Acta Crystallogr A 47:110–119CrossRefPubMedGoogle Scholar
  40. 40.
    Vriend G (1990) WHAT IF: a molecular modelling and drug design program. J Mol Graph 8:52–56CrossRefPubMedGoogle Scholar
  41. 41.
    Hooft RW, Vriend G, Sander C et al (1996) Errors in protein structures. Nature 381:272CrossRefPubMedGoogle Scholar
  42. 42.
    Nabuurs S, Spronk C, Krieger E et al (2004) Computational mechanical chemistry for drug discovery. Marcel Dekker, New York and Basel, pp 387–403Google Scholar
  43. 43.
    Lubkowski J, Dauter M, Aghaiypour K et al (2003) Atomic resolution structure of Erwinia chrysanthemi l-asparaginase. Acta Crystallogr D Biol Crystallogr 59:84–92CrossRefPubMedGoogle Scholar
  44. 44.
    Chen VB, Arendall WB III, Headd JJ et al (2010) MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr 66:12–21CrossRefPubMedGoogle Scholar
  45. 45.
    Davis IW, Murray LW, Richardson JS et al (2004) MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res 32:W615–W619CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Davis IW, Leaver-Fay A, Chen VB et al (2007) MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res 35:W375–W383CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Adams PD, Afonine PV, Bunkoczi G et al (2010) PHENIX: a comprehensive python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66:213–221CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Clowney L, Jain SC, Srinivasan A et al (1996) Geometric parameters in nucleic acids: nitrogenous bases. J Am Chem Soc 118:509–518CrossRefGoogle Scholar
  49. 49.
    Gelbin A, Schneider B, Clowney L et al (1996) Geometric parameters in nucleic acids: sugar and phosphate constituents. J Am Chem Soc 118:519–529CrossRefGoogle Scholar
  50. 50.
    Kleywegt GJ, Harris MR, Zou JY et al (2004) The Uppsala Electron-Density Server. Acta Crystallogr D Biol Crystallogr 60:2240–2249CrossRefPubMedGoogle Scholar
  51. 51.
    Schumacher MA, Tonthat NK, Lee J et al (2015) Structures of archaeal DNA segregation machinery reveal bacterial and eukaryotic linkages. Science 349:1120–1124CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Brünger AT (1992) The free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature 355:472–474CrossRefPubMedGoogle Scholar
  53. 53.
    Wlodawer A, Minor W, Dauter Z et al (2008) Protein crystallography for non-crystallographers or how to get the best (but not more) from the published macromolecular structures. FEBS J 275:1–21CrossRefPubMedGoogle Scholar
  54. 54.
    Zheng H, Chordia MD, Cooper DR et al (2014) Validation of metal-binding sites in macromolecular structures with the CheckMyMetal web server. Nat Protoc 9:156–170CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Macromolecular Crystallography LaboratoryNational Cancer InstituteFrederickUSA

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