Deconvolution of dynamic mechanical networks

TL;DR

This paper introduces a new dynamic deconvolution method to extract kinetic properties of components in complex mechanical networks from single-molecule experiments, enabling detailed analysis of conformational fluctuations and internal friction.

Contribution

We developed a dynamic deconvolution theory to determine intrinsic response functions of molecules within complex networks from equilibrium fluctuation data.

Findings

Successfully applied to simulated force spectroscopy data

Accurately extracted state-dependent protein diffusivity

Revealed physical insights into conformational fluctuations

Abstract

Time-resolved single-molecule biophysical experiments yield data that contain a wealth of dynamic information, in addition to the equilibrium distributions derived from histograms of the time series. In typical force spectroscopic setups the molecule is connected via linkers to a read-out device, forming a mechanically coupled dynamic network. Deconvolution of equilibrium distributions, filtering out the influence of the linkers, is a straightforward and common practice. We have developed an analogous dynamic deconvolution theory for the more challenging task of extracting kinetic properties of individual components in networks of arbitrary complexity and topology. Our method determines the intrinsic linear response functions of a given molecule in the network, describing the power spectrum of conformational fluctuations. The practicality of our approach is demonstrated for the particular case of a protein linked via DNA handles to two optically trapped beads at constant stretching force, which we mimic through Brownian dynamics simulations. Each well in the protein free energy landscape (corresponding to folded, unfolded, or possibly intermediate states) will have its own characteristic equilibrium fluctuations. The associated linear response function is rich in physical content, since it depends both on the shape of the well and its diffusivity---a measure of the internal friction arising from such processes like the transient breaking and reformation of bonds in the protein structure. Starting from the autocorrelation functions of the equilibrium bead fluctuations measured in this force clamp setup, we show how an experimentalist can accurately extract the state-dependent protein diffusivity using a straightforward two-step procedure.