Abstract: Allostery in protein-ligand and protein-protein interactions is of fundamental importance in biology and yet it is poorly understood at the molecular level. The phenomenological model developed by Monod, Wyman and Changeux in 1965 (MWC) is still the most widely used approach to model cooperative ligand binding, but it offers no molecular insight on the process. Allosteric interactions in proteins generally involve propagation of local structural changes through the protein to a remote site. Anisotropic energy transport is thought to couple the remote sites, but the nature of this process is unknown. We have studied the relationship between energy flow through the structure of a model system, bovine serum albumin (BSA) and allosteric interactions between remote ligand binding sites of the protein. We employ ultrafast infrared spectroscopy to probe the flow of energy through the protein backbone following excitation of a heater dye, malachite green (MG), bound to different drug binding sites in the protein. We observe anisotropic energy flow through the protein structure following input of thermal energy into the flexible ligand binding sites, without local heating of the rigid helix bundles that connect these sites. This efficient energy transport mechanism enables the allosteric propagation of binding energy through the connecting helix structures.
Prof. Christine Payne (404-385-3125)