Intermolecular interactions in biomolecular systems examined by mass spectrometry

With the development of electrospray and matrix-assisted laser desorption ionization, mass spectrometry (IMS) evolved into a powerful tool in the field of biochemistry. Whereas MS is primarily analytical in nature, an increasing number of MS research groups employ the method to address fundamental biochemical questions. Probing the interaction of noncovalendy bound molecules in the mass spectrometer is one of the most interesting MS-based experiments possible today, with the potential of making a significant contribution to the basic understanding of the structure and function of biochemical complexes. Here we review a number of current research efforts employing primarily MS techniques to investigate intermolecular interactions in biochemical systems. Examples chosen include the interaction of biomolecules with solvent molecules; interactions between nucleic-acid molecules, in particular, interactions in duplex and quadruplex structures; and interactions between proteins involved in neurodegenerative diseases. Finally we conclude by presenting a few examples of very large biomolecular assemblies in the mega-Dalton range analyzed by MS.