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bioRxiv · 10.1101/023796

Avoiding accuracy-limiting pitfalls in the study of protein-ligand interactions with isothermal titration calorimetry

Sarah E. Boyce·Joel Tellinghuisen·John D. Chodera
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Abstract

Isothermal titration calorimetry (ITC) can yield precise (3%) estimates of the thermodynamic parameters describing biomolecular association (affinity, enthalpy, and entropy), making it an indispensable tool for biochemistry and drug discovery. Surprisingly, interlaboratory comparisons suggest that errors of {bsim} 20% are common and widely underreported. Here, we show how to reduce precision- and accuracy-limiting errors while obtaining good estimates and minimizing material and time consumed by an experiment. We provide a simple spreadsheet that allows practitioners to identify precision-limiting operations during protocol design, track precision during the experiment, and propagate error to yield realistic final uncertainties.

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Sarah E. Boyce, Joel Tellinghuisen, John D. Chodera. 2015-08-03. Avoiding accuracy-limiting pitfalls in the study of protein-ligand interactions with isothermal titration calorimetry. https://doi.org/10.1101/023796

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