Forced Dissociation of a Biomolecular Complex
Date Issued
2009
Date
2009
Author(s)
Lin, Han-Jou
Abstract
The dissociation of a biomolecular complex under the action of constant force, constant loading rate, and periodic force is studied theoretically by Brownian dynamic simulation. We show that the celebrated Bell’s expression provides a good approximation for the bond dissociation rate when F/Fc<<1, where Fc is the maxima slope of the binding potential along the reaction coordinate. When 1-F/Fc<<1 the dissociation rate is better described by a generalized Garg’s form in which the potential derivative is expanded near Fc. We also show that a constant-force experiment is suitable for extracting the activation energy of the bond, a constant loading experiment is suitable to extract Fc, while time-periodic force can be applied to extract both bond dissociation rates at zero force and Fc.n the dissociation of a noncovalent biomolecular bond by external pulling, the bonded site is often connected to the force-acting site by a linkage. The role of the linkage stiffness on the rupture of a ligand-receptor complex under constant force is investigated by overdamped Langevin dynamics for the elastically coupled ligand and probe. The effects on the bond lifetime include effective ligand diffusivity, force fluctuations, and violation of adiabatic condition. The rupture rate declines with increasing linkage stiffness. For soft linkage, the effect associated with spring and probe can be ignored and the true rupture rate can be extracted. On the other hand, for stiff linkage, the diffusivity of the probe has to be accounted for and thus leads to a smaller rupture rate, dependent on the diffusivity ratio between probe and ligand. Nevertheless, the energy barrier height can be reasonably extracted by constant pulling experiments regardless of the linkage stiffness.he free energy landscape of a cooperative cluster of N parallel bonds, confined to the anchoring surface by springs of stiffness ks, is analytically constructed by the constant displacement method. We show that the dissociation kinetics of N parallel bonds can be modeled as an effective single bond with the activation energy being NEa essentially, where Ea is the intrinsic energy barrier of a single bond. The critical force Fc is shown to be proportional to N(ksEa)^0.5 and Fc/N is always small compared to the critical force associated with a single bond for soft springs. On the basis of the free energy landscape, the lifetime of adhesion clusters under constant force or loading rate can be obtained. Our theoretical analyses have been confirmed by Langevin dynamic simulations and demonstrate a new experimental method to obtain kinetic information. The influence of matrix elasticity on the critical force might be relevant to the preference of focal adhesion on rigid surfaces.
Subjects
Noncovalent bond
Pulling experiment
Type
thesis
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