Prediction of Catch-Slip Bond Transition of Kindlin2/β3 Integrin via Steered Molecular Dynamics Simulation.

Kindlin2 is believed to be crucial in integrin activation, which mediates the cell-extracellular matrix adhesion and signaling, but the mechanoregulation of the interaction between Kindlin2 and integrin remains unclear. Here, we performed the so-called "ramp-clamp" steered molecular dynamics simulation on the crystal structure of Kindlin2 bound with β3 integrin. The results showed that the complex had a better mechanical strength for its rupture force of about 200 pN under pulling with the velocity of 1 Å/ns, and was mechanostable for its conformational conservation under constant tensile force (≤60 pN). The catch-slip bond transition with a force threshold of 20 pN was demonstrated by the dissociation probability, the interaction energy, the interface H-bond number, and the force-induced allostery of the complex. This study might provide a novel insight into force-dependent Kindlin2/integrin-related signaling and its structural basis in cellular processes as well as a rational SMD-based computer strategy for predicting the structure-function relationship of the stretched complex.