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A new model for chemical shifts of amide hydrogens in proteins

  • Seongho Moon
  • David A. Case
Article

Abstract

We propose a new computational model to predict amide proton chemical shifts in proteins. In addition to the ring-current, susceptibility and electrostatic effects of earlier models, we add a hydrogen-bonding term based on density functional calculations of model peptide–peptide and peptide–water systems. Both distance and angular terms are included, and the results are rationalized in terms of natural bond orbital analysis of the interactions. Comparison to observed shifts for 15 proteins shows a significant improvement over existing structure-shift correlations. These additions are incorporated in a new version of the SHIFTS program.

Keywords

Chemical shifts Proteins Amide hydrogen 

Notes

Acknowledgments

This work was supported by NIH grant GM45811. We thank Jan Ziegler, Stephan Schwarzinger and Jan Jensen for helpful discussions.

References

  1. Asakura T, Taoka K, Demura M, Williamson MP (1995) The relationship between amide proton chemical shifts and secondary structure. J Biomol NMR 6:227–236CrossRefGoogle Scholar
  2. Barfield M (2002) Structural dependencies of interresidue scalar coupling h3JNC’ and donor 1H chemical shifts in the hydrogen bonding regions of proteins. J Am Chem Soc 124:4158–4168CrossRefGoogle Scholar
  3. Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652CrossRefADSGoogle Scholar
  4. Beger RD, Bolton PH (1997) Protein ϕ and ψ dihedral restraints determined from multidimensional hypersurface correlations of backbone chemical shifts and their use in the determination of protein tertiary structures. J Biomol NMR 10:129–142CrossRefGoogle Scholar
  5. Bohmann JA, Weinhold F, Farrar TC (1997) Natural chemical shielding analysis of nuclear magnetic resonance shielding tensors from gauge-including atomic orbital calculations. J Chem Phys 107:1173–1184CrossRefADSGoogle Scholar
  6. Buckingham AD, Schaefer T, Schneider WG (1960) Solvent effects in nuclear magnetic resonance spectra. J Chem Phys 32:1227–1233CrossRefADSGoogle Scholar
  7. Case DA, Cheatham TE III, Darden T, Gohlke H, Luo R, Merz KM Jr, Onufriev A, Simmerling C, Wang B, Woods R (2005) The Amber biomolecular simulation programs. J Comput Chem 26:1668–1688CrossRefGoogle Scholar
  8. Cornilescu G, Delaglio F, Bax A (1999) Protein backbone angle restraints from searching a database for chemical shift and sequence homology. J Biomol NMR 13:289–302CrossRefGoogle Scholar
  9. Cui Q, Karplus M (2000) Molecular properties from combined QM/MM methods 2. Chemical shifts in large molecules. J Phys Chem B 104:3721–3743CrossRefGoogle Scholar
  10. 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
  11. Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, Zhang W, Yang R, Cieplak P, Luo R, Lee T (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J Comput Chem 24:1999–2012CrossRefGoogle Scholar
  12. Frisch MJ, Trucks GW, Schlegel HB, Gill PMW, Johnson BG, Robb JA, Cheeseman JR, Keith TA, Petersson GA, Montgomery JA, Raghavachari K, Al-Laham MA, Zakrzewski VG, Ortiz JV, Foresman JB, Cioslowski J, Stefanov BB, Nanayakkara A, Challacombe M, Peng CY, Ayala PY, Chen W, Wong MW, Andres JL, Replogle ES, Gomperts R, Martin RL, Fox DJ, Binkley JS, Defrees DJ, Baker J, Stewart JP, Head-Gordon M, Gonzalez C, Pople JA (1998) Gaussian 98 (Revision A9). Gaussian Inc, Pittsburgh PAGoogle Scholar
  13. Haigh CW, Mallion RB (1980) Ring current theories in nuclear magnetic resonance. Prog NMR Spectr 13:303–344CrossRefGoogle Scholar
  14. 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
  15. Jeng M-F, Campbell AP, Begley T, Holmgren A, Case DA, Wright PE, Dyson HJ (1994) High-resolution solution structures of oxidized and reduced Escherichia coli thioredoxin. Structure 2:853–868CrossRefGoogle Scholar
  16. Jorgensen WL, Chandrasekhar J, Madura J, Klein ML (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926–935CrossRefADSGoogle Scholar
  17. Le H, Oldfield E (1994) Correlation between N NMR chemical shifts in proteins and secondary structure. J Biomol NMR 4:341–348CrossRefGoogle Scholar
  18. Le H, Oldfield E (1996) Ab initio studies of amide-N chemical shifts in dipeptides: applications to protein NMR spectroscopy. J Phys Chem 100:16423–16428CrossRefGoogle Scholar
  19. McConnell HM (1957) Theory of nuclear magnetic shielding in molecules I Long-range dipolar shielding of protons. J Chem Phys 27:226–229CrossRefADSGoogle Scholar
  20. Meiler J (2003) PROSHIFT: protein chemical shift prediction using artificial neural networks. J Biomol NMR 26:25–37CrossRefGoogle Scholar
  21. Meiler J, Maier W, Will M, Meusinger R (2002) Using neural networks for 13C NMR chemical shift prediction-comparison with traditional methods. J Magn Reson 157:242–252CrossRefADSGoogle Scholar
  22. Moon S, Case DA (2006) A comparison of quantum chemical models for calculating NMR shielding parameters in peptides: mixed basis set and ONIOM methods combined with a complete basis set extrapolation. J Comput Chem 27:825–836CrossRefGoogle Scholar
  23. Neal S, Nip AM, Zhang H, Wishart DS (2003) Rapid and accurate calculation of protein 1H, 13C and 15N chemical shifts. J Biomol NMR 26:215–240CrossRefGoogle Scholar
  24. Ösapay K, Case DA (1991) A new analysis of proton chemical shifts in proteins. J Am Chem Soc 113:9436–9444CrossRefGoogle Scholar
  25. Parker LL, Houk AR, Jensen JH (2006) Cooperative hydrogen bonding effects are key determinants of backbone amide proton chemical shifts in proteins. J Am Chem Soc 128:9863–9872CrossRefGoogle Scholar
  26. Pearson JG, Le H, Sanders LK, Godbout N, Havlin RH, Oldfield E (1997) Predicting chemical shifts in proteins: structure refinement of valine residues by using ab initio and empirical geometry optimizations. J Am Chem Soc 119:11941–11950CrossRefGoogle Scholar
  27. Perdew JP, Wang Y (1992) Accurate and simple analytic representation of the electron-gas correlation energy. Phys Rev B 45:13244–13249Google Scholar
  28. Polshakov VI, Birdsall B, Feeney J (1999) Characterization of rates of ring-flipping in trimethoprim in its ternary complexes with Lactobacillus casei dihydrofolate reductase and coenzyme analogues. Biochemistry 38:15962–15969CrossRefGoogle Scholar
  29. Redfield C, Dobson CM (1990) H NMR studies of human lysozyme: spectral assignment and comparison with hen lysozyme. Biochemistry 29:7201–7214CrossRefGoogle Scholar
  30. Rumelhart DE, McClelland J (1986) Parallel distrbuted processing. MIT Press, BostonGoogle Scholar
  31. Sharma Y, Kwon OY, Brooks B, Tjandra N (2002) An ab initio study of amide proton shift tensor dependence on local protein structure. J Am Chem Soc 124:327–335CrossRefGoogle Scholar
  32. Sitkoff D, Case DA (1997) Density functional calculations of proton chemical shifts in model peptides. J Am Chem Soc 119:12262–12273CrossRefGoogle Scholar
  33. Spera S, Bax A (1991) Empirical correlation between protein backbone conformation and Cα and Cβ C nuclear magnetic resonance chemical shifts. J Am Chem Soc 113:5490–5492CrossRefGoogle Scholar
  34. Wishart DS, Case DA (2001) Use of chemical shifts in macromolecular structure determination. Meth Enzymol 338:3–34CrossRefGoogle Scholar
  35. Xu XP, Case DA (2001) Automated prediction of N, Cα, Cβ and C’ chemical shifts in proteins using a density functional database. J Biomol NMR 21:321–333CrossRefGoogle Scholar
  36. Xu XP, Case DA (2002) Probing multiple effects on N, Cα, Cβ and C’ chemical shifts in peptides using density functional theory. Biopolymers 65:408–423CrossRefGoogle Scholar
  37. Zupan J, Gasteiger J (1993) Neural networks for chemists. VCH Verlagsgesellschaft mbH, WeinheimGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  1. 1.Department of Molecular BiologyThe Scripps Research InstituteLa JollaUSA

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