Probing protein-protein interactions by dynamic force correlated spectroscopy (FCS)

TL;DR

This paper introduces a formalism for single-molecule dynamic force spectroscopy to analyze protein-protein interactions, revealing how internal protein dynamics influence unbinding lifetimes through a novel joint distribution approach.

Contribution

It develops a new theoretical framework for analyzing unbinding lifetimes in protein complexes, incorporating internal relaxation dynamics and proposing experiments to resolve these effects.

Findings

The joint distribution of unbinding times is non-Poissonian.

Internal protein dynamics significantly affect unbinding lifetime distributions.

The formalism applies to wormlike chain models of proteins.

Abstract

We develop a formalism for single molecule dynamic force spectroscopy to map the energy landscape of protein-protein complex ($P_1$$P_2$). The joint distribution $P(\tau_1,\tau_2)$ of unbinding lifetimes $\tau_1$ and $\tau_2$ measurable in a compression-tension cycle, which accounts for the internal relaxation dynamics of the proteins under tension, shows that the histogram of $\tau_1$ is not Poissonian. The theory is applied to the forced unbinding of protein $P_1$, modeled as a wormlike chain, from $P_1$$P_2$. We propose a new class of experiments which can resolve the effect of internal protein dynamics on the unbinding lifetimes.