Inhibitor trapping

Inhibitor trapping, also known as ligand trapping or ligand entrapment, pertains to an inhibition mechanism in which a small molecule ligand becomes enclosed and locked within the structure of the protein target. During this process, the protein molecule acts as a trap, effectively immobilizing the small molecule within it. Simultaneously, the ligand confines the protein in a specific inhibited conformation by significantly reducing its dynamic movements. Inhibitor trapping leads to a substantial reduction in the dissociation rate of the ligand, resulting in increased binding affinity and activity.

Ligand entrapment distinguishes itself from other models of inhibition, where the binding affinity is often evaluated by estimating the change in free binding energy caused by the transfer of the ligand from the solution to the protein's binding site. In contrast, the inhibitor trapping model suggests that the affinity of the inhibitor is influences by the protein's conformational dynamics, which determine whether the ligand will remain bound within its binding site