Journal of Biomolecular NMR

, Volume 48, Issue 1, pp 23–30 | Cite as

Sequential nearest-neighbor effects on computed 13Cα chemical shifts

  • Jorge A. Vila
  • Pedro Serrano
  • Kurt Wüthrich
  • Harold A. Scheraga
Article

Abstract

To evaluate sequential nearest-neighbor effects on quantum-chemical calculations of 13Cα chemical shifts, we selected the structure of the nucleic acid binding (NAB) protein from the SARS coronavirus determined by NMR in solution (PDB id 2K87). NAB is a 116-residue α/β protein, which contains 9 prolines and has 50% of its residues located in loops and turns. Overall, the results presented here show that sizeable nearest-neighbor effects are seen only for residues preceding proline, where Pro introduces an overestimation, on average, of 1.73 ppm in the computed 13Cα chemical shifts. A new ensemble of 20 conformers representing the NMR structure of the NAB, which was calculated with an input containing backbone torsion angle constraints derived from the theoretical 13Cα chemical shifts as supplementary data to the NOE distance constraints, exhibits very similar topology and comparable agreement with the NOE constraints as the published NMR structure. However, the two structures differ in the patterns of differences between observed and computed 13Cα chemical shifts, Δca,i, for the individual residues along the sequence. This indicates that the Δca,i -values for the NAB protein are primarily a consequence of the limited sampling by the bundles of 20 conformers used, as in common practice, to represent the two NMR structures, rather than of local flaws in the structures.

Keywords

Quantum-chemical calculation of 13Cα- chemical shifts NMR structures of proteins Sampling of conformation space 

References

  1. Aramini JM, Sharma S, Huang YJ, Swapna GVT, Ho CK, Shetty K, Cunningham K, Ma L-C, Zhao L, Owens LA, Jiang M, Xiao R, Liu J, Baran MC, Acton TB, Rost B, Montelione GT (2008) Solution NMR structure of the SOS response protein YnzC from Bacillus subtilis. Proteins Struct Funct Bioinformatics 72:526–530CrossRefGoogle Scholar
  2. Carugo O, Pongor S (2001) A normalized root-mean distance for comparing protein three-dimensional structures. Protein Sci 10:1470–1473CrossRefGoogle Scholar
  3. Chesnut DB, Moore KD (1989) Locally dense basis-sets for chemical-shift calculations. J Comp Chem 10:648–659CrossRefGoogle Scholar
  4. Cornilescu G, Marquardt JL, Ottiger M, Bax A (1998) Validation of protein structure from anisotropic carbonyl chemical shifts in a dilute liquid crystalline phase. J Am Chem Soc 120:6836–6837CrossRefGoogle Scholar
  5. de Dios AC, Pearson JG, Oldfield E (1993) Secondary and tertiary structural effects on protein NMR chemical shifts: An ab initio approach. Science 260:1491–1496CrossRefADSGoogle Scholar
  6. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA,Cheeseman JR, Zakrzewski VG, Montgomery JA, Stratmann REJr, Burant JC, Dapprich S, Millam JM, Daniels AD, Kudin KN,Strain MC, Farkas O, Tomasi J, Barone V, Cossi M, Cammi R,Mennucci B, Pomelli C, Adamo C, Clifford S, Ochterski J,Petersson GA, Ayala PY, Cui Q, Morokuma K, Malick DK,Rabuck AD, Raghavachari K, Foresman JB, Cioslowski J, OrtizV, Baboul AG, Stefanov BB, Liu G, Liashenko A, Piskorz P,Komaromi I, Gomperts R, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Gonzalez C, Chal-lacombe M, Gill PMW, Johnson B, Chen W, Wong MW, AndresJL, Gonzalez C, Head-Gordon M, Replogle ES, Pople JA (2004) Gaussian 03, Revision E.01, Gaussian, Inc., Wallingford CTGoogle Scholar
  7. Havlin RH, Le H, Laws DD, de Dios AC, Oldfield E (1997) An ab initio quantum chemical investigation of carbon–13 NMR shielding tensors in glycine, alanine, valine, isoleucine, serine, and threonine: Comparisons between helical and sheet tensors, and effects of χ1 on shielding. J Am Chem Soc 119:11951–11958CrossRefGoogle Scholar
  8. Iwadate M, Asakura T, Williamson MP (1999) Cα and Cβ carbon–13 chemical shifts in proteins from an empirical database. J Biomol NMR 13:199–211CrossRefGoogle Scholar
  9. Koradi R, Billeter M, Güntert P (2000) Point-centered domain decomposition for parallel molecular dynamics simulation. Comp Physics Commun 124:139–147CrossRefADSMATHGoogle Scholar
  10. Kuszewski J, Qin JA, Gronenborn AM, Clore GM (1995) The impact on direct refinement against 13Cα and 13Cβ chemical shifts on protein structure determination by NMR. J Magn Reson B 106:92–96CrossRefGoogle Scholar
  11. Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Cryst 26:283–291CrossRefGoogle Scholar
  12. Luginbühl P, Szyperski T, Wüthrich K (1995) Statistical basis for the use of 13Cα chemical shift in protein structure determination. J Magn Reson 109:229–233CrossRefGoogle Scholar
  13. Luginbühl P, Güntert P, Billeter M, Wüthrich K (1997) The new program OPAL for molecular dynamics simulations and energy refinements of biological macromolecules. J Biomol NMR 8:136–146Google Scholar
  14. Martin OA, Villegas ME, Vila JA, Scheraga HA (2010) Analysis of 13Cα and 13Cβ chemical shifts of cysteine and cystine residues in proteins: a quantum chemical approach. J Biomol NMR 46:217–225CrossRefGoogle Scholar
  15. Némethy G, Gibson KD, Palmer KA, Yoon CN, Paterlini G, Zagari A, Rumsey S, Scheraga HA (1992) Energy parameters in polypeptides. 10. Improved geometrical parameters and nonbonded interactions for use in the ECEPP/3 algorithm, with application to praline-containing peptides. J Phys Chem 96:11941–11950CrossRefGoogle Scholar
  16. Pearson JG, Le H, Sanders LK, Godbout N, Havlin RH, Oldfield EJ (1997) Predicting chemical shifts in proteins: structure refinement of valine residues by using ab initio and empirical geometry optimizations. J Am Chem Soc 119:11951–11958CrossRefGoogle Scholar
  17. Schwarzinger S, Kroon GJA, Foss TR, Chung J, Wright PE, Dyson HJ (2001) Sequence-dependent correction of random coil NMR chemical shifts. J Am Chem Soc 123:2970–2978CrossRefGoogle Scholar
  18. Serrano P, Johnson MA, Chatterjee A, Neuman B, Joseph JS, Buchmeier MJ, Kuhn P, Wüthrich K (2009) NMR structure of the nucleic acid-binding domain of the SARS coronavirus nonstructural protein 3. J Virol 83:12998–13008CrossRefGoogle Scholar
  19. Spera S, Bax A (1991) Empirical correlation between protein backbone conformation and Cα and Cβ 13C nuclear magnetic resonance chemical shifts. J Am Chem Soc 113:5490–5492CrossRefGoogle Scholar
  20. Sun H, Sanders LK, Oldfield E (2002) Carbon-13 NMR shielding in the twenty common amino acids: comparisons with experimental results in proteins. J Am Chem Soc 124:5486–5495CrossRefGoogle Scholar
  21. Vijay-Kumar S, Bugg CE, Cook WJ (1987) Structure of ubiquitin refined at 1.8 Å resolution. J Mol Biol 194:531–544CrossRefGoogle Scholar
  22. Vila JA, Scheraga HA (2008) Factors affecting the use of 13Cα chemical shifts to determine, refine, and validate protein structures. Proteins: Struct, Funct, Bioinformatics 71:641–654CrossRefGoogle Scholar
  23. Vila JA, Scheraga HA (2009) Assessing the accuracy of protein structures by quantum mechanical computations of 13Cα chemical shifts (2009a). Acc Chem Res 42:1545–1553CrossRefGoogle Scholar
  24. Vila JA, Ripoll DR, Scheraga HA (2007a) Use of 13Cα chemical shifts in protein structure determination. J Phys Chem B 111:6577–6585CrossRefGoogle Scholar
  25. Vila JA, Villegas ME, Baldoni HA, Scheraga HA (2007b) Predicting 13Cα chemical shifts for validation of protein structures. J Biomol NMR 38:221–235CrossRefGoogle Scholar
  26. Vila JA, Arnautova YA, Scheraga HA (2008a) Use of 13Cα chemical shifts for accurate determination of β-sheet structures in solution. Proc Natl Acad Sci USA 105:1891–1896CrossRefADSGoogle Scholar
  27. Vila JA, Baldoni HA, Scheraga HA (2008b) Performance of density functional models to reproduce observed 13Cα chemical shifts of proteins in solution. J Comp Chem 38:884–892Google Scholar
  28. Vila JA, Arnautova YA, Martin OA, Scheraga HA (2009) Quantum-Mechanics-Derived 13Cα Chemical Shift Server (CheShift) for protein structure validation. Proc Natl Acad Sci USA 106:16972–16977CrossRefADSGoogle Scholar
  29. Villegas ME, Vila JA, Scheraga HA (2007) Effects of side–chain orientation on the 13C chemical shifts of antiparallel β–sheet model peptides. J Biomol NMR 37:137–146CrossRefGoogle Scholar
  30. Wang Y, Jardetzky O (2002) Investigation of the neighboring residue effects on protein chemical shifts. J Am Chem Soc 124:14075–14084CrossRefGoogle Scholar
  31. Wishart D, Bigam CG, Holm A, Hodges RS, Sykes BD (1995a) 1H, 13C and 15N random coil NMR chemical shifts of the common amino acids. I. Investigation of nearest-neigbor effects. J Biomol NMR 5:67–81CrossRefGoogle Scholar
  32. Wishart D, Bigam CG, Yao J, Abildgaard F, Dyson H, Oldfield E, Markley J, Sykes B (1995b) 1H, 13C and 15N chemical shift referencing in biomolecular NMR. J Biomol NMR 6:135–140CrossRefGoogle Scholar
  33. Wüthrich K (1986) NMR of proteins and nucleic acids. Wiley, USAGoogle Scholar
  34. Xu XP, Case DA (2001) Automatic prediction of 15 N, 13Cα, 13Cβ and 13C′ chemical shifts in proteins using a density functional database. J Biomol NMR 21:321–333CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Jorge A. Vila
    • 1
    • 2
  • Pedro Serrano
    • 3
    • 4
  • Kurt Wüthrich
    • 3
    • 4
  • Harold A. Scheraga
    • 1
  1. 1.Baker Laboratory of Chemistry and Chemical BiologyCornell UniversityIthacaUSA
  2. 2.Universidad Nacional de San LuisInstituto de Matemática Aplicada San LuisCONICETEjército de Los AndesArgentina
  3. 3.Department of Molecular BiologyThe Scripps Research InstituteLa JollaUSA
  4. 4.Skaggs Institute for Chemical BiologyThe Scripps Research InstituteLa JollaUSA

Personalised recommendations