an inorganic language for biological self-assembly: controlling protein-protein interactions through metal coordination chemistry
This research proposal presents a powerful new approach for the chemical control of protein-protein interactions (PPI's). PPI's are central to nearly all cellular processes. Despite extensive research efforts, however, the ability to predict or manipulate natural PPI's or engineer artificial ones remains a great challenge, owing to the fact that PPI's are guided by the superposition of many weak, non-covalent bonds spread over large surfaces. Our goal is to utili:te the strength, directionality and selectivity of metal-ligand interactions to control PPI's, thereby achieving affinity and specificity without requiring extensive binding surfaces. Armed with exciting preliminary observations and a diverse suite of experimental approaches, we propose to establish general design principles for the control of PPI's through coordination chemistry, and apply these principles to the construction of robust, functional bioassemblies and the control of cellular signaling pathways.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.