As　revealed　by　previous　experiments,　protein　mechanical　stability　can　be　effectively　regulated　by　ligand　binding　with　the　binding　site　distant　from　the　force-bearing　region.　However,　the　mechanism　for　such　long-range　allosteric　control　of　protein　mechanics　is　still　largely　unknown.　In　this　work,　we　use　protein　topology-based　elastic　network　model　(ENM)　and　all-atomic　steered　molecular　dynamics　(SMD)　simulations　to　study　the　impact　of　ligand　binding　on　protein　mechanical　stability　in　two　systems,　i.e.,　GB1　and　CheY-binding　P2-domain　of　CheA　(CBDCheA).　Both　ENM　and　SMD　results　show　that　the　ligand　binding　has　considerable　and　negligible　effects　on　the　mechanical　stability　of　these　two　proteins,　respectively.　These　results　are　consistent　with　the　experimental　observations.　A　physical　mechanism　for　the　enhancement　of　protein　mechanical　stability　was　then　proposed:　the　correlated　deformations　of　the　force　bearing　region　and　the　binding　site　are　handcuffed　by　the　binding　of　ligand.　The　handcuff　effect　suppresses　the　propagation　of　internal　force　in　the　force　bearing　region,　thus　improving　the　resistance　to　the　loading　force.　Our　study　indicates　that　ENM　method　can　effectively　identify　the　structure　motifs　allosterically　related　to　the　deformation　in　the　force　bearing　region,　as　well　as　the　force　propagation　pathway　within　the　structure　of　the　studied　proteins.　Hence,　it　should　be　helpful　to　understand　the　molecular　origin　of　the　different　mechanical　properties　in　response　to　ligand　binding　for　GB1　and　CBDCheA.　Published　under　license　by　AIP　Publishing.