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Dependence of Work on the Pulling Speed in Mechanical Ligand Unbinding.

ABSTRACT: 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 ∼ 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 ∼ c₁ 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.

SUBMITTER: Pham HA

PROVIDER: S-EPMC8389893 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Dependence of Work on the Pulling Speed in Mechanical Ligand Unbinding.

Pham Hong An HA Truong Duc Toan DT Li Mai Suan MS

The journal of physical chemistry. B 20210722 30

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. ...[more]

PMID: 34292743

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