Facilitator Models of Weak Binding in Protein-Protein Interactions

Pairwise interactions are intuitive to our understanding on protein-ligand binding; however in vivo this is rarely true. Most intracellular proteins operate in a highly cooperative manner to perform tasks ranging from metabolic turnover to intricate signaling regulation. In some cases, one substrate needs to simultaneously interact with more than one binding partner to carry out faithful signal transductions. While one of these binding partners is the determinant of such signal transduction, it can share very similar tertiary structure with the other but might differ in functional role and abundance. Motivated by this observation, we explore the physical consequences of the mere steric presence of a non-specific ligand, the “competitor”, crowding the surface of a “target” ligand. The specific interaction occurs between the protein and the “target” ligand, which explores the same surface as well, albeit for its unique binding site. A simple lattice model incorporating these elements along with the natural rules of exclusion and hopping reveals the regimes for when recruitment (turnover) or residence (transition state stabilization) are favored. Exploration of the search dynamics of the two ligands along the protein surface provides further insight.