Accuracy of Optimized Chemical-exchange Parameters Derived by Fitting CPMG R 2 Dispersion Profiles when R 2 0a ≠ R 2 0b (original) (raw)

Abstract

The transverse relaxation rate, R 2, measured as a function of the effective field (R 2 dispersion) using a Carr-Purcell-Meiboom-Gill (CPMG) pulse train, is well suited to detect conformational exchange in proteins. The dispersion data are commonly fitted by a two-site (sites a and b) exchange model with four parameters: the relative population, p a, the difference in chemical shifts of the two sites, δω, the correlation time for exchange, τex, and the intrinsic relaxation rate (i.e., transverse relaxation rate in the absence of chemical exchange), R 02 . Although the intrinsic relaxation rates of the two sites, R 0a2 and R 0b2 , can differ, they are normally assumed to be the same (i.e., R 0a2 = R 0b2 = R 02 ) when fitting dispersion data. The purpose of this investigation is to determine the magnitudes of the errors in the optimized exchange parameters that are introduced by the assumption that R 0a2 = R 0b2 . In order to accomplish this goal, we first generated synthetic constant-time CPMG R 2 dispersion data assuming two-site exchange with R 0a2 ≠ R 0b2 , and then fitted the synthetic data assuming two-site exchange with R 02 = R 0a2 = R 0b2 . Although all the synthetic data generated assuming R 0a2 ≠ R 0b2 were well fitted (assuming R 0a2 = R 0b2 ), the optimized values of p a and τ ex differed from their true values, whereas the optimized values of δω values did not. A theoretical analysis using the Carver–Richards equation explains these results, and yields simple, general equations for estimating the magnitudes of the errors in the optimized parameters, as a function of ( R 0a2 − R 0b2 ).

Access this article

Log in via an institution

Subscribe and save

• Get 10 units per month
• Download Article/Chapter or eBook
• 1 Unit = 1 Article or 1 Chapter
• Cancel anytime Subscribe now

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

References

• H. Beach R. Cole M.L. Gill J.P. Loria (2005)J. Am. Chem. Soc. 127 9167–9176Occurrence Handle10.1021/ja0514949
  Article Google Scholar
• J.P. Carver R.E. Richards (1972)J. Magn. Reson. 6 89–105
  Google Scholar
• J. Cavanagh W.J. Fairbrother A.G. PalmerSuffix3rd N.J. Skelton (1996) Protein NMR Spectroscopy Academic Press San Diego 135
  Google Scholar
• W.Y. Choy Z. Zhou Y.W. Bai L.E. Kay (2004)J. Am. Chem. Soc. 127 5066–5072Occurrence Handle10.1021/ja042560u
  Article Google Scholar
• D.G. Davis M.E. Perlman R.E. London (1994)J. Magn. Reson B 104 266–275
  Google Scholar
• M.J. Grey C. Wang A.G. PalmerSuffix3rd (2003)J. Am. Chem. Soc., 125 14325–14335Occurrence Handle10.1021/ja0367389
  Article Google Scholar
• R. Ishima P.T. Wingfield S.J. Stahl J.D. Kaufman D.A. Torchia (1998)J. Am. Chem. Soc. 120 10534–10542Occurrence Handle10.1021/ja981546c
  Article Google Scholar
• R. Ishima D.A. Torchia (2003)J. Biomol. NMR 25 243–348Occurrence Handle10.1023/A:1022851228405
  Article Google Scholar
• R. Ishima D.A. Torchia (2005)J. Biomol. NMR 32 41–54Occurrence Handle10.1007/s10858-005-3593-z
  Article Google Scholar
• J. Jen (1978)J. Magn. Reson. 30 111–128
  Google Scholar
• D. Korzhnev K. Kloiber L.E. Kay (2004a)J. Am. Chem. Soc. 126 7320–7329Occurrence Handle10.1021/ja049968b
  Article Google Scholar
• D.M. Korzhnev X. Salvatella M. Vendruscolo A.A. Di Nardo A.R. Davidson C.M. Dobson L.E. Kay (2004b)Nature 430 586–590Occurrence Handle10.1038/nature02655Occurrence Handle2004Natur.430..586K
  Article ADS Google Scholar
• J.P. Loria M. Rance A.G. PalmerSuffix3rd (1999)J. Am. Chem. Soc. 121 2331–2332Occurrence Handle10.1021/ja983961a
  Article Google Scholar
• H.M. McConnell (1958)J. Chem. Phys. 28 430–431Occurrence Handle10.1063/1.1744152Occurrence Handle1958JChPh..28..430M
  Article ADS Google Scholar
• O. Millet J.P. Loria C.D. Kroenke M. Pons A.G. Palmer (2000)J. Am. Chem. Soc. 122 2867–2877Occurrence Handle10.1021/ja993511y
  Article Google Scholar
• F.A.A. Mulder N.R. Skrynnikov B. Hon F.W. Dahlquist L.E. Kay (2001)J. Am. Chem. Soc. 123 967–975Occurrence Handle10.1021/ja003447g
  Article Google Scholar
• V.Y. Orekhov K.V. Pervushin A.S. Arseniev (1994)Eur. J. Biochem. 219 887–896Occurrence Handle10.1111/j.1432-1033.1994.tb18570.x
  Article Google Scholar
• A.G. Palmer C.D. Kroenke J.P. Loria (2001)Methods Enzymol. 339 204–238Occurrence Handle10.1016/S0076-6879(01)39315-1
  Article Google Scholar
• N.R. Skrynnikov F.A.A. Mulder B. Hon F.W. Dahlquist L.E. Kay (2001)J. Am. Chem. Soc. 123 4556–4566Occurrence Handle10.1021/ja004179p
  Article Google Scholar
• M. Tollinger N.R. Skrynnikov F.A.A. Mulder J.D. Forman-Kay L.E. Kay (2001)J. Am. Chem. Soc. 123 11341–11352Occurrence Handle10.1021/ja011300z
  Article Google Scholar
• R.L. Vold S.O. Chan (1972)J. Chem. Phys. 56 28–31Occurrence Handle10.1063/1.1676859Occurrence Handle1972JChPh..56...28V
  Article ADS Google Scholar
• C. Wang M.J. Grey A.G. PalmerSuffix3rd (2001)J. Biomol. NMR 21 361–366Occurrence Handle10.1023/A:1013328206498
  Article Google Scholar
• D.E. Woessner (1960)J. Chem. Phys. 35 41–48Occurrence Handle10.1063/1.1731931Occurrence Handle1961JChPh..35...41W
  Article ADS Google Scholar
• S. Yao S.J. Headey D.W. Keizer L.A. Bach R.S. Norton (2004)Biochemistry 43 11187–11195Occurrence Handle10.1021/bi049456+
  Article Google Scholar

Download references

Author information

Authors and Affiliations

1. Molecular Structural Biology Unit, >National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Rm 109, 30 Convent Dr., Bethesda, MD, 20892-4307, USA
   Rieko Ishima & Dennis A. Torchia
2. Department of Structural Biology, University of Pittsburgh, Biomedical Science Tower 3, 3501 5th Avenue, Pittsburgh, PA, 15260, USA
   Rieko Ishima

Authors

1. Rieko Ishima
   You can also search for this author inPubMed Google Scholar
2. Dennis A. Torchia
   You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toRieko Ishima.

Rights and permissions

About this article

Cite this article

Ishima, R., Torchia, D.A. Accuracy of Optimized Chemical-exchange Parameters Derived by Fitting CPMG R 2 Dispersion Profiles when R 0a2 ≠ R 0b2 .J Biomol NMR 34, 209–219 (2006). https://doi.org/10.1007/s10858-005-6226-7

Download citation

• Received: 19 October 2005
• Accepted: 23 December 2005
• Issue Date: April 2006
• DOI: https://doi.org/10.1007/s10858-005-6226-7

Keywords