Determination of Protein−Ligand Association Thermochemistry Using Variable-Temperature Nanoelectrospray Mass Spectrometry

A novel temperature-controlled nanoelectrospray (nanoES) device, interfaced with a Fourier transform ion cyclotron resonance mass spectrometer, is used to measure the association constants, K assoc, for a series of protein−carbohydrate complexes at solution temperatures ranging from 5 to 40 °C. From a van't Hoff analysis of the K assoc values, the enthalpies and entropies of association (ΔH assoc, ΔS assoc) at 25 °C are determined. The nanoES/mass spectrometry-derived thermodynamic parameters are in agreement with values previously determined by isothermal titration calorimetry.