Abstract
Two problems that are often overlooked in studies employing nonlinear least-squares techniques for parameter estimation are confidence-interval estimation and propagation. When the parameters are correlated, the variance space and consequently the confidence intervals are nonlinear and asymmetrical. The presented mathematical method for the evaluation of confidence intervals and error propagation addresses these problems. The examples employed to demonstrate these methods include linear least-squares and the nonlinear least-squares analysis of ligand-binding problems, such as hormone receptor interactions and oxygen binding to human hemoglobin. The mathematical procedures have proven very useful for analyzing the molecular mechanism of cooperativity in human hemoglobin (Johnson, M. L., and G. K. Ackers, 1982. Biochemistry 21:201-211).
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ackers G. K., Halvorson H. R. The linkage between oxygenation and subunit dissociation in human hemoglobin. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4312–4316. doi: 10.1073/pnas.71.11.4312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ackers G. K., Johnson M. L. Linked functions in allosteric proteins. Extension of the concerted (MWC) model for ligand-linked subunit assembly and its application to human hemoglobins. J Mol Biol. 1981 Apr 25;147(4):559–582. doi: 10.1016/0022-2836(81)90400-9. [DOI] [PubMed] [Google Scholar]
- Ackers G. K., Johnson M. L., Mills F. C., Halvorson H. R., Shapiro S. The linkage between oxygenation and subunit dissociation in human hemoglobin. Consequences for the analysis of oxygenation curves. Biochemistry. 1975 Nov 18;14(23):5128–5134. doi: 10.1021/bi00694a017. [DOI] [PubMed] [Google Scholar]
- Ackers G. K., Johnson M. L., Mills F. C., IP S. H. Energetics of oxygenation-linked subunit interactions in human hemoglobin. Biochem Biophys Res Commun. 1976 Mar 8;69(1):135–142. doi: 10.1016/s0006-291x(76)80283-5. [DOI] [PubMed] [Google Scholar]
- Atha D. H., Johnson M. L., Riggs A. F. The linkage between oxygenation and subunit association in human hemoglobin Kansas. Concentration dependence of the oxygen binding equilibria. J Biol Chem. 1979 Dec 25;254(24):12390–12398. [PubMed] [Google Scholar]
- Endrenyi L., Kwong F. H. Some problems of estimating macromolecule-ligand binding parameters. Acta Biol Med Ger. 1973;31(4):495–505. [PubMed] [Google Scholar]
- Ip S. H., Johnson M. L., Ackers G. K. Kinetics of deoxyhemoglobin subunit dissociation determined by haptoglobin binding: estimation of the equilibrium constant from forward and reverse rates. Biochemistry. 1976 Feb 10;15(3):654–660. doi: 10.1021/bi00648a032. [DOI] [PubMed] [Google Scholar]
- Johnson M. L., Ackers G. K. Resolvability of Adair constants from oxygenation curves measured at low hemoglobin concentration. Biophys Chem. 1977 Jun;7(1):77–80. doi: 10.1016/0301-4622(77)87017-8. [DOI] [PubMed] [Google Scholar]
- Johnson M. L., Ackers G. K. Thermodynamic analysis of human hemoglobins in terms of the Perutz mechanism: extensions of the Szabo--Karplus model to include subunit assembly. Biochemistry. 1982 Jan 19;21(2):201–211. doi: 10.1021/bi00531a001. [DOI] [PubMed] [Google Scholar]
- Johnson M. L., Correia J. J., Yphantis D. A., Halvorson H. R. Analysis of data from the analytical ultracentrifuge by nonlinear least-squares techniques. Biophys J. 1981 Dec;36(3):575–588. doi: 10.1016/S0006-3495(81)84753-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson M. L., Halvorson H. R., Ackers G. K. Oxygenation-linked subunit interactions in human hemoglobin: analysis of linkage functions for constituent energy terms. Biochemistry. 1976 Nov 30;15(24):5363–5371. doi: 10.1021/bi00669a024. [DOI] [PubMed] [Google Scholar]
- Mills F. C., Johnson M. L., Ackers G. K. Oxygenation-linked subunit interactions in human hemoglobin: experimental studies on the concentration dependence of oxygenation curves. Biochemistry. 1976 Nov 30;15(24):5350–5362. doi: 10.1021/bi00669a023. [DOI] [PubMed] [Google Scholar]