# Quantitative Integration of FRET and Molecular Dynamics for Modeling Flexible Peptides

## TL;DR

This paper combines FRET experiments and molecular dynamics simulations to study the behavior of flexible peptides and validate their structural and kinetic properties.

## Contribution

The study introduces an improved force field parameterization for Dbo-labeled aspartic residues, enabling accurate modeling of fluorophore-labeled peptides.

## Key findings

- Simulations reproduce FRET-derived end-to-end distances with less than 5% deviation for (GS)n peptides.
- Looping kinetics agree with experimental contact formation rates after viscosity correction.
- The work establishes a quantitative link between structural ensembles and FRET experiments.

## Abstract

Flexible protein regions, often enriched in glycine-
and serine-rich
segments, play a central role in biomolecular dynamics and function.
The combination of time-resolved fluorescence resonance energy transfer
(FRET) spectroscopy and molecular dynamics simulations provides a
powerful framework to characterize these motions at atomic resolution.
In this work, we investigate the conformational and kinetic properties
of Trp-(GS)
n
-Dbo and Trp-(PP)
n
-Dbo peptides (n = 0, 1, 2, 3) in
aqueous solution using microsecond-scale MD simulations, informed
by an improved description of the Dbo-labeled aspartic residue compatible
with the G54A7 force field. The simulations quantitatively reproduce
experimental end-to-end distances derived from FRET measurements,
with deviations below 5% for all (GS)
n
peptides, and correctly capture the systematic relationship between
chain flexibility and fluorophore separation. Analysis of looping
kinetics further shows quantitative agreement with experimentally
measured contact formation rates after viscosity correction, supporting
a diffusion-controlled mechanism for intrachain contact formation.
Together, these results establish a consistent, quantitative link
between structural ensembles, dynamical observables, and FRET experiments,
and provide benchmark data for modeling fluorophore-labeled peptides
and intrinsically disordered protein segments.