Effects of force on facilitated protein dissociation

Protein-DNA interactions depend on the conformation of DNA, so binding/unbinding kinetics may be altered by applied forces; classically, protein unbinding is accelerated and binding is inhibited as force increases. Additionally, certain proteins exhibit concentration-dependent dissociation rates, where proteins in solution compete to facilitate protein dissociation from DNA. Together, facilitated dissociation (FD) and force can lead to diverse dissociation behaviors including “slip bonds”, where dissociation rates decrease with force, and “catch bonds”, where dissociation rates increase with force. We investigate these combined effects via coarse-grained simulation. We reproduce concentration-dependent rates that are observed experimentally and explore how force can alter these binding kinetics. We observe catch bonds when protein binding is strongly coupled to the force, while the force dependence of protein unbinding is relatively weak. Slip bonds occur under opposite conditions. Transitions between these different bonds occur when force effects on binding and unbinding compete. Thus, applied force may regulate protein-DNA interactions by inhibiting FD by coupling protein exchange rates to DNA conformations.