Multiple barriers in forced rupture of protein complexes

TL;DR

This paper analyzes the rupture force behavior in biomolecular complexes, proposing criteria to distinguish between single and multiple barrier unbinding mechanisms based on force spectroscopy data.

Contribution

It introduces a criterion to determine whether biomolecular unbinding involves a single or multiple energy barriers using rupture force data.

Findings

Biotin-ligand complexes show evidence of multiple barrier crossing.

The exponent $ u$ is less than 0.5 for certain complexes, indicating multiple barriers.

A new criterion helps interpret dynamic force spectroscopy results.

Abstract

Curvatures in the most probable rupture force ($f^*$) versus log-loading rate ($\log{r_f}$) observed in dynamic force spectroscopy (DFS) on biomolecular complexes are interpreted using a one-dimensional free energy profile with multiple barriers or a single barrier with force-dependent transition state. Here, we provide a criterion to select one scenario over another. If the rupture dynamics occurs by crossing a single barrier in a physical free energy profile describing unbinding, the exponent $\nu$, from $(1- f^*/f_c)^{1/\nu}\sim(\log r_f)$ with $f_c$ being a critical force in the absence of force, is restricted to $0.5 \leq \nu \leq 1$. For biotin-ligand complexes and leukocyte-associated antigen-1 bound to intercellular adhesion molecules, which display large curvature in the DFS data, fits to experimental data yield $\nu<0.5$, suggesting that ligand unbinding is associated with multiple-barrier crossing.