Mass Spectrometry for Structural Biology
Identification and detailed structural characterisation of protein complexes is vital for predicting protein functions and understanding the principles of cellular regulation. Many protein assemblies of interest are intractable by conventional structural biology methods (such as NMR spectroscopy and X-ray crystallography) and hence complementary low resolution approaches such as MS are increasingly sought to provide structural information.
Much of our MS development centres on application of ion mobility-mass spectrometry (IM-MS), a hybrid analytical method which provides not only mass but shape information for an ion. IM-MS can potentially define protein identity, stoichiometry, size, structural arrangement and subunit interactions in a single experiment to derive low resolution structural models of interacting proteins.
This research aims to optimise successful detection and analysis of non-covalent protein complexes of a wide range of structures and binding interactions by IM-MS. In addition, aspects of this project can involve development of theoretical methods to generate model protein structures for comparison with experimentally derived measurements, to not only assist IM-MS analysis, but have implications for protein structure prediction in general. The ultimate aim of this work is to utilise IM-MS methods in combination with other biophysical techniques (such as NMR, SAXS, microscopy) to support the emerging field of integrative structural biology where many pieces of data are combined to generate a complete picture of a protein assembly.