RT Journal Article
SR Electronic
T1 Rigorous equations for isothermal titration calorimetry: theoretical and practical consequences
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 512780
DO 10.1101/512780
A1 Philippe Dumas
YR 2019
UL http://biorxiv.org/content/early/2019/01/06/512780.abstract
AB New mathematical methods have been developed for processing titration curves (TC) obtained from Isothermal Titration Calorimetry (ITC). Exact TC equations for the usual multi-injection method (MIM), or for the single-injection method (SIM) with continuous injection, were derived by taking into account rigorously the effect of dilution resulting from the titration process. Several practical consequences of these results are discussed. An exact fit of a TC can thus be obtained, even with large injected volumes leading to important dilution. All available programs show systematic differences with the exact results, NanoAnalyze from TA being significantly more accurate. The results are currently being incorporated into AFFINImeter from S4SD. It is also examined how certain multi-step mechanisms are in fact thermodynamically equivalent to the one-step association/dissociation mechanism. They will thus never explain any “atypical” TC not showing the classical sigmoid shape. Although only a single pair of parameters (Kd and ΔH) can explain an experimental TC compatible with the one-step mechanism, an infinite number of parameters explain equally well the same data with such an equivalent multi-step mechanism. An explicit link between the two sets of parameters is given. A parallel with the concept of gauge invariance in physics is proposed.