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Coussens NP, Schuck P, Zhao H. Strategies for assessing proton linkage to bimolecular interactions by global analysis of isothermal titration calorimetry data. J Chem Thermodyn. 2012;52:95-107doi: 10.1016/j.jct.2012.02.008.
Coussens, N. P., Schuck, P., & Zhao, H. (2012). Strategies for assessing proton linkage to bimolecular interactions by global analysis of isothermal titration calorimetry data. The Journal of chemical thermodynamics, 5295-107. https://doi.org/10.1016/j.jct.2012.02.008
Coussens, Nathan P, et al. "Strategies for assessing proton linkage to bimolecular interactions by global analysis of isothermal titration calorimetry data." The Journal of chemical thermodynamics vol. 52 (2012): 95-107. doi: https://doi.org/10.1016/j.jct.2012.02.008
Coussens NP, Schuck P, Zhao H. Strategies for assessing proton linkage to bimolecular interactions by global analysis of isothermal titration calorimetry data. J Chem Thermodyn. 2012 Sep 01;52:95-107. doi: 10.1016/j.jct.2012.02.008. PMID: 22773848; PMCID: PMC3388511.
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J Chem Thermodyn. 2012 Sep 01;52:95-107. doi: 10.1016/j.jct.2012.02.008.

Strategies for assessing proton linkage to bimolecular interactions by global analysis of isothermal titration calorimetry data.

The Journal of chemical thermodynamics

Nathan P Coussens, Peter Schuck, Huaying Zhao

Affiliations

  1. Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A.

PMID: 22773848 PMCID: PMC3388511 DOI: 10.1016/j.jct.2012.02.008

Abstract

Isothermal titration calorimetry (ITC) is a traditional and powerful method for studying the linkage of ligand binding to proton uptake or release. The theoretical framework has been developed for more than two decades and numerous applications have appeared. In the current work, we explored strategic aspects of experimental design. To this end, we simulated families of ITC data sets that embed different strategies with regard to the number of experiments, range of experimental pH, buffer ionization enthalpy, and temperature. We then re-analyzed the families of data sets in the context of global analysis, employing a proton linkage binding model implemented in the global data analysis platform SEDPHAT, and examined the information content of all data sets by a detailed statistical error analysis of the parameter estimates. In particular, we studied the impact of different assumptions about the knowledge of the exact concentrations of the components, which in practice presents an experimental limitation for many systems. For example, the uncertainty in concentration may reflect imperfectly known extinction coefficients and stock concentrations or may account for different extents of partial inactivation when working with proteins at different pH values. Our results show that the global analysis can yield reliable estimates of the thermodynamic parameters for intrinsic binding and protonation, and that in the context of the global analysis the exact molecular component concentrations may not be required. Additionally, a comparison of data from different experimental strategies illustrates the benefit of conducting experiments at a range of temperatures.

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