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Dependence of Work on the Pulling Speed in Mechanical Ligand Unbinding

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journal contribution
posted on 22.07.2021, 16:35 by Hong An Pham, Duc Toan Truong, Mai Suan Li
In single-molecule force spectroscopy, the rupture force Fmax 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, Fmax ∼ ln­(V). Recently, it has been found that non-equilibrium work W is better than Fmax 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, Wc1 ln­(V) + c2 ln2(V), where c1 and c2 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.