Mechanical affinity as a new metrics to evaluate binding events

Abstract

Binding affinity is measured by dissociation constant, K</sub>d</sub> , which uses concentration as units. The universal concentration units facilitate direct comparison of affinities for different binding events. However, K</sub>d</sub> is a thermodynamic parameter, which lacks kinetic information of a binding event. In addition, K</sub>d</sub> 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.