Cooperative Free Energy: Induced Protein-Protein Interactions and Cooperative Solvation in Ternary Complexes.

ABSTRACT: Protein-protein interactions (PPIs) play an essential role in biological processes. Molecules that stabilize or induce PPIs in ternary complexes have received growing attention for their therapeutic potential in engaging "undruggable" targets and their high selectivity. Here, we investigate the thermodynamics of the cooperative phenomenon in ternary complexes. The thermodynamics of cooperativity are characterized by the cooperative free energy, which comprises induced PPIs, cooperative solvation free energy, ligand-associated geometric free-energy costs, and gas-phase correlation. Importantly, the induced PPIs only account for the binding affinity between stabilized conformations of the protein partners, i.e., the free-energy change associated with the conformational transition during prot

SUBMITTER: Chen SY 

PROVIDER: S-EPMC12424184 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature