Our research program is designed to answer the following two questions:
- What is the relationship between condensed- and gas-phase structure (& other properties)?
- How can biological molecules be made to adopt condensed-phase properties in the gas phase?
Our research is of both fundamental and applied interest.
Understanding of the forces controlling protein structure and dynamics is essential to understand and manipulate biological systems. We are particularly interested in determining the role of non-covalent interactions, such as protein-water interactions, on protein structure and stability. From an applications perspective, mass spectrometry is now routinely used to analyze biological systems. While in some cases solution-phase structural properties appear to be retained in the gas phase, other studies indicate little or no correlation. Thus, although gas-phase analysis shows great promise in areas like drug binding assays, the unresolved relationship between mass spectrometry and solution-phase studies greatly restricts its utility. Our studies are designed to bridge between solution and the gas phase.
We are combining trapping mass spectrometry with laser spectroscopy in order to characterize the structure, stability and dynamics of biomolecules and biomolecular complexes in a controlled gas-phase environment. Native biological systems are highly complex, and their state depends on the interplay of numerous factors. Our gas-phase studies promise valuable simplification by examining how specific environmental factors affect biomolecules and their complexes. We seek to answer key questions such as: How does water affect the conformation of biomolecules and their non-covalent complexes? Are bound water molecules necessary to maintain the fold of a particular enzyme or to stabilize intermediates? If so, how many water molecules? What is the influence of other ligands, protons or metal ions?