This approach has been successfully applied to protein-ligand and protein-protein interactions, demonstrating both versatility and effectiveness. For example, it has been used to study the binding of benzene to L99A T4 lysozyme, revealing enhanced flexibility in the binding pockets compared to the EN model . The method also accurately reproduced the conformational flexibility and hydration levels around the zinc-binding site of Copper-zinc superoxide dismutase, aligning well with results from QM/MM MD simulations. Additionally, it identified the destabilizing allosteric effect of the G93A mutation on the zinc-binding site (100) and probed the mechanical stability of several biomolecular systems , including SARS-CoV-2 variants in complex with a potent nanobody. Specific mutations were found to significantly influence the formation and rupture of native and non-native contacts under high mechanical loads, impacting the mechanical stability of these complexes. Furthermore, the hyper-mechanostability of bone sialoprotein binding protein in complex with fibrinogen-𝛼 was explored, revealing rupture forces exceeding 2 nN and highlighting key residue interactions that resist mechanical stress (102). The CG potential is available via the server at .