Biomolecules often undergo conformational changes when interacting with binding partners or substrates, encompassing both induced fit and conformational selection mechanisms. These structural changes can occur at binding sites or be distributed across the structure. The significant role of allostery in enzyme function, where an allosteric modulator molecule binds to sites distal to the active site, has been recognized for decades . Recent advances combining experimental data with advanced modeling methods have revealed structural details of allosteric mechanisms . Evolutionary coupling (EC) based on sequence covariance analysis has also been utilized to enhance enzyme activities by perturbing allosteric networks with mutations distant from their active sites .