Dependence of Work on the Pulling Speed in Mechanical Ligand Unbinding

In single-molecule force spectroscopy, the rupture force F-max required for mechanical unfolding of a biomolecule or for pulling a ligand out of a binding site depends on the pulling speed V and, in the linear Bell-Evans regime, F-max similar to ln(V). Recently, it has been found that non-equilibrium work W is better than F-max in describing relative ligand binding affinity, but the dependence of W on V remains unknown. In this paper, we developed an analytical theory showing that in the linear regime, W similar to c(1) ln(V) + c(2) ln(2)(V), where c(1) and c(2) are constants. This quadratic dependence was also confirmed by all-atom steered molecular dynamics simulations of protein-ligand complexes. Although our theory was developed for ligand unbinding, it is also applicable to other processes, such as mechanical unfolding of proteins and other biomolecules, due to its universality.

Automated summary

The paper investigates the relationship between non-equilibrium work and pulling speed in single-molecule force spectroscopy, showing a quadratic dependence of work on ln(V) and ln(2)(V) in the linear regime. This theory was confirmed through molecular dynamics simulations of protein-ligand complexes, indicating its applicability to various processes in biomolecular mechanics.