Nanosecond chain dynamics of single-stranded nucleic acids

TL;DR

This study combines advanced single-molecule techniques and modeling to reveal that short single-stranded nucleic acids undergo extremely rapid conformational dynamics in the 10-ns range, primarily influenced by solvent friction.

Contribution

The paper introduces a novel integrated experimental and computational approach to accurately characterize the fast chain dynamics of single-stranded nucleic acids.

Findings

Chain reconfiguration times are around 10 nanoseconds.

Dynamics are dominated by solvent friction with negligible internal friction.

Structural ensembles closely match experimental data.

Abstract

The conformational dynamics of single-stranded nucleic acids are fundamental for nucleic acid folding and function. However, their elementary chain dynamics have been difficult to resolve experimentally. Here we employ a combination of single-molecule F\"orster resonance energy transfer, nanosecond fluorescence correlation spectroscopy, fluorescence lifetime analysis, and nanophotonic enhancement to determine the conformational ensembles and rapid chain dynamics of short single-stranded nucleic acids in solution. To interpret the experimental results in terms of end-to-end distance dynamics, we utilize the hierarchical chain growth approach, simple polymer models, and refinement with Bayesian inference of ensembles to generate structural ensembles that closely align with the experimental data. The resulting chain reconfiguration times are exceedingly rapid, in the 10-ns range. Solvent viscosity-dependent measurements indicate that these dynamics of single-stranded nucleic acids exhibit negligible internal friction and are thus dominated by solvent friction. Our results provide a detailed view of the conformational distributions and rapid dynamics of single-stranded nucleic acids.