Proteins play a key role in important biological processes, and as such, are key targets for newly developed drugs. The three-dimensional model of a protein can be analyzed to find promising sites for potential drug binding, but determining the structure of a single protein typically takes months or even years. In order to speed up the drug design process and to take advantage of the possibilities presented by protein-protein interactions, this project will make use of techniques currently employed in the analysis of large numbers of proteins in a cell, tissue, or organism (“proteomics”). Specifically, emerging cross-linking techniques using formaldehyde and newly synthesized reagents will be employed to preserve biologically active protein-protein interactions in living cells or in solution for subsequent analysis by mass spectrometry (MS). The team will develop algorithms and software for the interpretation of the MS data in order to determine 3D structural protein models and validate their approach by the analysis of protein-protein interactions involved. Understanding these interactions can help assist in the development of potential lead drug candidates.