Dynamic polarizability of macromolecules for single-molecule optical biosensing

TL;DR

This paper presents a new computational method to predict the dynamic polarizability of macromolecules from their atomic structure, enabling noninvasive optical biosensing of molecular dynamics.

Contribution

It introduces an efficient approach linking atomic configurations to polarizability, facilitating structural insights from optical measurements of single molecules.

Findings

Method accurately predicts polarizability changes over time

Quantifies thermal and functional motion effects on polarizability

Connects molecular dynamics simulations to optical sensing data

Abstract

The structural dynamics of macromolecules is important for most microbiological processes, from protein folding to the origins of neurodegenerative disorders. Noninvasive measurements of these dynamics are highly challenging. Recently, optical sensors have been shown to allow noninvasive time-resolved measurements of the dynamic polarizability of single-molecules. Here we introduce a method to efficiently predict the dynamic polarizability from the atomic configuration of a given macromolecule. This provides a means to connect the measured dynamic polarizability to the underlying structure of the molecule, and therefore to connect temporal measurements to structural dynamics. To illustrate the methodology we calculate the change in polarizability as a function of time based on conformations extracted from molecular dynamics simulations and using different conformations of motor proteins solved crystalographically. This allows us to quantify the magnitude of the changes in polarizablity due to thermal and functional motions.