Skip to main content
SpringerLink
Log in

Structural dynamics of protein backbone φ angles: extended molecular dynamics simulations versus experimental 3 J scalar couplings

  • Communication
  • Published:
Journal of Biomolecular NMR Aims and scope Submit manuscript

Abstract

3 J scalar couplings report on the conformational averaging of backbone φ angles in peptides and proteins, and therefore represent a potentially powerful tool for studying the details of both structure and dynamics in solution. We have compared an extensive experimental dataset with J-couplings predicted from unrestrained molecular dynamics simulation using enhanced sampling available from accelerated molecular dynamics or using long timescale trajectories (200 ns). The dynamic fluctuations predicted to be present along the backbone, in agreement with residual dipolar coupling analysis, are compatible with the experimental 3 J scalar couplings providing a slightly better reproduction of these experimental parameters than a high-resolution static structure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  • Bernado P, Blackledge M (2004a) Anisotropic small amplitude peptide plane dynamics in proteins from residual dipolar couplings. J Am Chem Soc 126:4907–4920

    Article  Google Scholar 

  • Bernado P, Blackledge M (2004b) Local dynamic amplitudes on the protein backbone from dipolar couplings: toward the elucidation of slower motions in biomolecules. J Am Chem Soc 126:7760–7761

    Article  Google Scholar 

  • Bouvignies G, Bernado P, Meier S, Cho K, Grzesiek S, Brüschweiler R, Blackledge M (2005) Identification of slow correlated motions in proteins using residual dipolar and hydrogen-bond scalar couplings. Proc Natl Acad Sci USA 102:13885–13890

    Article  ADS  Google Scholar 

  • Bouvignies G, Markwick P, Brüschweiler R, Blackledge M (2006) Simultaneous determination of protein backbone structure and dynamics from residual dipolar couplings. J Am Chem Soc 128:15100–15101

    Article  Google Scholar 

  • Brüschweiler R, Case D (1994) Adding harmonic motion to the Karplus equation for spin–spin coupling. J Am Chem Soc 116:11199–11200

    Article  Google Scholar 

  • Case DA (2000) Interpretation of chemical shifts and coupling constants in macromolecules. Curr Opin Struct Biol 10:197–203

    Article  Google Scholar 

  • Case DA, Scheurer C, Brüschweiler R (2000) Static and dynamic effects on vicinal scalar J couplings in proteins and peptides: a MD/DFT analysis. J Am Chem Soc 122:10390–10397

    Article  Google Scholar 

  • Case DA, Cheatham TE 3rd, Darden T, Gohlke H, Luo R, Merz KM Jr, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) The amber biomolecular simulation programs. J Comput Chem 26:1668–1688

    Article  Google Scholar 

  • Clore GM, Schwieters CD (2004) How much backbone motion in ubiquitin is required to account for dipolar coupling data measured in multiple alignment media as assessed by independent cross-validation? J Am Chem Soc 126:2923–2938

    Article  Google Scholar 

  • Hamelberg D, Mongan J, McCammon JA (2004) Accelerated molecular dynamics: a promising and efficient simulation method for biomolecules. J Chem Phys 120:11919–11929

    Article  ADS  Google Scholar 

  • Hoch JC, Dobson CM, Karplus M (1985) Vicinal coupling constants and protein dynamics. Biochemistry 24:3831–3841

    Article  Google Scholar 

  • Hornak V, Okur A, Rizzo RC, Simmerling C (2006) HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations. Proc Natl Acad Sci U S A 103:915–920

    Article  ADS  Google Scholar 

  • Hu J-S, Bax A (1996) Measurement of three-bond 13C-13C J couplings between carbonyl and carbonyl/carboxyl carbons in isotopically enriched proteins. J Am Chem Soc 118:8170–8171

    Article  Google Scholar 

  • Karplus M (1959) Contact electron-spin coupling of nuclear magnetic moments. J Chem Phys 30:11–15

    Article  ADS  Google Scholar 

  • Lakomek NA, Walter KF, Fares C, Lange OF, de Groot BL, Grubmuller H, Brüschweiler R, Munk A, Becker S, Meiler J, Griesinger C (2008) Self-consistent residual dipolar coupling based model-free analysis for the robust determination of nanosecond to microsecond protein dynamics. J Biomol NMR 41:139–155

    Article  Google Scholar 

  • Losonczi JA, Prestegard JH (1998) Improved dilute bicelle solutions for high-resolution NMR of biological macromolecules. J Biomol NMR 12:447–451

    Article  Google Scholar 

  • Markwick PR, Bouvignies G, Blackledge M (2007) Exploring multiple timescale motions in protein GB3 using accelerated molecular dynamics and NMR spectroscopy. J Am Chem Soc 129:4724–4730

    Article  Google Scholar 

  • Meiler J, Prompers JJ, Peti W, Griesinger C, Brüschweiler R (2001) Model-free approach to the dynamic interpretation of residual dipolar couplings in globular proteins. J Am Chem Soc 123:6098–6107

    Article  Google Scholar 

  • Mittermaier A, Kay LE (2006) New tools provide new insights in NMR studies of protein dynamics. Science 312:224–228

    Article  ADS  Google Scholar 

  • Salmon L, Bouvignies G, Markwick P, Lakomek N, Showalter S, Li DW, Walter K, Griesinger C, Brüschweiler R, Blackledge M (2009) Protein conformational flexibility from structure-free analysis of NMR dipolar couplings: quantitative and absolute determination of backbone motion in ubiquitin. Angew Chem Int Ed Engl 48:4154–4157

    Article  Google Scholar 

  • Schmidt JM, Blumel M, Lohr F, Ruterjans H (1999) Self-consistent (3)J coupling analysis for the joint calibration of Karplus coefficients and evaluation of torsion angles. J Biomol NMR 14:1–12

    Article  Google Scholar 

  • Showalter S, Brüschweiler R (2007a) Validation of molecular dynamics simulations of biomolecules using NMR spin relaxation as benchmarks: application to the AMBER99SB force field. J Chem Theory Comput 3:961–975

    Article  Google Scholar 

  • Showalter SA, Brüschweiler R (2007b) Quantitative molecular ensemble interpretation of NMR dipolar couplings without restraints. J Am Chem Soc 129:4158–4159

    Article  Google Scholar 

  • Tjandra N, Bax A (1997) Direct measurement of distances and angles in biomolecules by NMR in a dilute liquid crystalline medium. Science 278:1111–1114

    Article  ADS  Google Scholar 

  • Tolman JR (2002) A novel approach to the retrieval of structural and dynamic information from residual dipolar couplings using several oriented media in biomolecular NMR spectroscopy. J Am Chem Soc 124:12020–12030

    Article  Google Scholar 

  • Tolman J, Flanagan J, Kennedy M, Prestegard J (1995) Nuclear magnetic dipole interactions in field-oriented proteins: information for structure determination in solution. Proc Natl Acad Sci USA 92:9279–9283

    Article  ADS  Google Scholar 

  • Tolman JR, Flanagan JM, Kennedy MA, Prestegard JH (1997) NMR evidence for slow collective motions in cyanometmyoglobin. Nat Struct Biol 4:292–297

    Article  Google Scholar 

  • Ulmer TS, Ramirez BE, Delaglio F, Bax A (2003) Evaluation of backbone proton positions and dynamics in a small protein by liquid crystal NMR spectroscopy. J Am Chem Soc 125:9179–9191

    Article  Google Scholar 

  • Vogeli B, Ying J, Grishaev A, Bax A (2007) Limits on variations in protein backbone dynamics from precise measurements of scalar couplings. J Am Chem Soc 129:9377–9385

    Article  Google Scholar 

  • Vogeli B, Yao L, Bax A (2008) Protein backbone motions viewed by intraresidue and sequential HN-Halpha residual dipolar couplings. J Biomol NMR 41:17–28

    Article  Google Scholar 

  • Yao L, Vogeli B, Torchia DA, Bax A (2008a) Simultaneous NMR study of protein structure and dynamics using conservative mutagenesis. J Phys Chem B 112:6045–6056

    Article  Google Scholar 

  • Yao L, Vogeli B, Ying J, Bax A (2008b) NMR determination of amide N-h equilibrium bond length from concerted dipolar coupling measurements. J Am Chem Soc 130:16518–16520

    Article  Google Scholar 

Download references

Acknowledgments

G. B. received a grant from the CEA. This work was supported by EU through EU-NMR JRA3 and through ANR NT05-4_42781 and by the National Science Foundation (MCB-0918362). The authors would like to thank Dr. Frank Löhr for helpful discussions.

Author information

Authors and Affiliations

  1. Protein Dynamics and Flexibility, Institut de Biologie Structurale Jean-Pierre Ebel UMR 5075, CNRS/CEA/UJF, 41 Rue Jules Horowitz, 38027, Grenoble, France

    Phineus R. L. Markwick, Guillaume Bouvignies & Martin Blackledge

  2. Department of Chemistry and Biochemistry, NHMFL, Florida State University, Tallahassee, FL, 32306, USA

    Scott A. Showalter & Rafael Brüschweiler

Authors
  1. Phineus R. L. Markwick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Scott A. Showalter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guillaume Bouvignies
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rafael Brüschweiler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martin Blackledge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Rafael Brüschweiler or Martin Blackledge.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Markwick, P.R.L., Showalter, S.A., Bouvignies, G. et al. Structural dynamics of protein backbone φ angles: extended molecular dynamics simulations versus experimental 3 J scalar couplings. J Biomol NMR 45, 17–21 (2009). https://doi.org/10.1007/s10858-009-9341-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10858-009-9341-z

Keywords

Search

Navigation