Mechanical affinity as a new metrics to evaluate binding events

Binding affinity is measured by dissociation constant, Kd, which uses concentration as units. The universal concentration units facilitate direct comparison of affinities for different binding events. However, Kd is a thermodynamic parameter, which lacks kinetic information of a binding event. In addition, Kd does not reveal the mechanical property of the binding, which emerges as a critical element for many physiologically significant processes such as DNA replication, RNA transcription, and protein translation. Here we propose a new parameter, mechanical affinity, to delineate kinetic and mechanical features of a binding event. The mechanical affinity is equivalent to the work required to dissemble the chemical binding between a ligand and a receptor. During this process, it must cover dissipated heat that originates from the relative movement between a ligand and a receptor. Because dissipated heat varies with unfolding direction or rate of mechanical perturbation, the mechanical affinity is a function of these two variables. Screening of chemicals using rupture force of a ligand-receptor complex or mechanical affinity is discussed at the end of this review. The interrogation on the mechanical interaction between a ligand and a receptor provides a new perspective not available in conventional thermodynamic evaluation of binding processes.