The study of large biopolymer complexes in solution and the gas phase using electrospray ionization-FTICR mass spectrometry

Electrospray ionization (ESI) can transfer large biopolymers and many noncovalently bound complexes into the gas phase and to preserve specific noncovalent biomolecular associations for subsequent mass spectrometric analysis. Although a number of details of the ESI process remain a subject of debate, it is now incontestable that many weak associations can survive transfer to the gas phase and are stable for periods of at least seconds. In this presentation, the application of ESI-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry methods for the study of large biopolymers and their noncovalent complexes will be described. It will also be shown that competitive binding studies can be used to quickly establish relative binding affinities in solution, allowing combinatorial libraries to be rapidly screened. After measurements of the intact complex, dissociation studies can be conducted to probe the structure of the individual constituents of complexes. Studies comparing the relative stabilities of protein-ligand complexes in solution and desolvated in the gas phase will also be presented, and discussed from both fundamental and analytical perspectives.