The advantage of global fitting of data involving complex linked reactions
Language English Country United States Media print
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
GM 775551
NIGMS NIH HHS - United States
- MeSH
- Calorimetry MeSH
- Rabbits MeSH
- Monte Carlo Method MeSH
- Least-Squares Analysis MeSH
- Pyruvate Kinase chemistry metabolism MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- Pyruvate Kinase MeSH
In this chapter, we demonstrate the advantage of the simultaneous multicurve nonlinear least-squares analysis over that of the conventional single-curve analysis. Fitting results are subjected to thorough Monte Carlo analysis for rigorous assessment of confidence intervals and parameter correlations. The comparison is performed on a practical example of simulated steady-state reaction kinetics complemented with isothermal calorimetry (ITC) data resembling allosteric behavior of rabbit muscle pyruvate kinase (RMPK). Global analysis improves accuracy and confidence limits of model parameters. Cross-correlation between parameters is also reduced with accompanying enhancement of the model-testing power. This becomes especially important for validation of models with "difficult" highly cross-correlated parameters. We show how proper experimental design and critical evaluation of data can improve the chance of differentiating models.
References provided by Crossref.org
In vivo kinetics of U4/U6·U5 tri-snRNP formation in Cajal bodies