Perturbations such as mutations, post-translational modifications, and biomolecular interactions promote functional alterations in proteins, often without significant structural changes. Such changes in the ensemble properties and the associated function, even at a site distant from the site that is perturbed, rely on the extent of energetic or thermodynamic coupling between residues. Here, integrating statistical mechanical modeling, experiments and simulations, we showcase the importance of residue-level thermodynamic coupling free energies and their connection to ensemble dynamics. We show that coupling free energy estimates carry critical information on structural transitions, functional sites, and even provide an avenue to map allosteric communication routes. The effect of perturbations dissipates exponentially from the site of mutation, with the largest effect mediated by charged residues due to nontrivial conformational redistributions in the native ensemble. We reinforce our computational findings by extending our coupling analysis to two bilobed proteins — FF34 of p190A RhoGAP, and Cytidine Repressor (CytR) ligand binding domain. We demonstrate that non-optimal electrostatics at the FF34 interface contribute to a marginally stable, conformationally heterogeneous protein with minimal coupling between the two lobes, which are drastically altered upon a single charge reversal perturbation. We also connect the anisotropic distribution of coupling free energies across the two sub-domains in CytR to conformational heterogeneity and dynamics, which possibly influence its function. Our work thus emphasizes how thermodynamic coupling free energies can provide unique insights into the structural-energetic basis of its behavior, with implications in protein design.