Multiple barriers in forced rupture of protein complexes

Abstract

Curvatures in the most probable rupture force ($f^{\ast }$) 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 $(1-f^{\ast }/f_c{)}^{1/\nu }\sim (\log r_f)$ with $f_c$ being a critical force in the absence of force, is restricted to $0.5\le \nu \le 1$. 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.

8 pages, 5 figures

References in corpus (3)

• Forced-unfolding and force-quench refolding of RNA hairpins
• Measuring the energy landscape roughness and the transition state location of biomolecules using single molecule mechanical unfolding experiments
• Compaction and tensile forces determine the accuracy of folding landscape parameters from single molecule pulling experiments

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• Evidence of disorder in biological molecules from single molecule pulling experiments
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• Extracting folding landscape characteristics of biomolecules using mechanical forces
• Force-Induced Unzipping Transitions in an Athermal Crowded Environment