Unraveling multi-state molecular dynamics in single-molecule FRET experiments. I. Theory of FRET-lines

@article{Barth2022UnravelingMM,
  title={Unraveling multi-state molecular dynamics in single-molecule FRET experiments. I. Theory of FRET-lines},
  author={Anders Barth and O. A. Opanasyuk and Thomas O. Peulen and Suren Felekyan and Stanislav Kalinin and Hugo Sanabria and Claus A. M. Seidel},
  journal={The Journal of Chemical Physics},
  year={2022},
  volume={156}
}
Conformational dynamics of biomolecules are of fundamental importance for their function. Single-molecule studies of Förster Resonance Energy Transfer (smFRET) between a tethered donor and acceptor dye pair are a powerful tool to investigate the structure and dynamics of labeled molecules. However, capturing and quantifying conformational dynamics in intensity-based smFRET experiments remains challenging when the dynamics occur on the sub-millisecond timescale. The method of multiparameter… 

Identification and Quantification of Within-Burst Dynamics in Singly-Labeled Single-Molecule Fluorescence Lifetime Experiments

TLDR
The analytical framework provided in this work paves the way for extracting a full picture of the energy landscape for the coordinate probed by fluorescence-lifetime based single-molecule measurements.

Reliability and accuracy of single-molecule FRET studies for characterization of structural dynamics and distances in proteins

TLDR
A worldwide blind study involving 19 labs to assess the uncertainty of FRET experiments for proteins with respect to the measured FRET efficiency histograms, determination of distances, and the detection and quantification of structural dynamics.

Multi-parameter photon-by-photon hidden Markov modeling

TLDR
The importance of using mpH2MM to decouple FRET dynamics caused by conformational changes from photophysical transitions in confocal-based smFRET measurements of a DNA hairpin, the maltose binding protein, MalE, and the type-III secretion system effector, YopO from Yersinia species are shown.

Fuzzy Supertertiary Interactions within PSD-95 Enable Ligand Binding

TLDR
The hybrid structural models reveal how the supertertiary context of PDZ3 enables recognition of this critical synaptic ligand in PSD-95.

References

SHOWING 1-10 OF 126 REFERENCES

Detection of structural dynamics by FRET: a photon distribution and fluorescence lifetime analysis of systems with multiple states.

TLDR
An analysis procedure for multiparameter fluorescence detection is presented, where intensity-derived FRET efficiency is correlated with the fluorescence lifetime of the donor quenched by FRET, and these new techniques are compared with fluorescence correlation spectroscopy.

Theory of the energy transfer efficiency and fluorescence lifetime distribution in single-molecule FRET

TLDR
The theory of the joint distribution of FRET efficiencies and fluorescence lifetimes determined from bins (or bursts) of photons, which leads to an analytic result for a two-state system interconverting on a timescale slower than the interphoton time and to an efficient simulation algorithm for multistate dynamics.

Analysis of Fluorescence Lifetime and Energy Transfer Efficiency in Single-Molecule Photon Trajectories of Fast-Folding Proteins.

TLDR
Analysis methods to utilize fluorescence lifetime information from single-molecule FRET experiments are presented, and these methods are applied to three fast-folding, two-state proteins.

Covalent dye attachment influences the dynamics and conformational properties of flexible peptides

TLDR
The approach combining experimental and in silico methods provides a benchmark for the simulations and reveals the significant effect that fluorescence labeling can have on the conformational dynamics of small biomolecules, at least for inherently flexible short peptides.

Excited-state annihilation reduces power dependence of single-molecule FRET experiments.

TLDR
It is shown that excited-state annihilation processes are an essential cause of singlet-singlet annihilation, and both SSA and STA have a pronounced effect on the overall FRET process and reduce the power dependence of the observed FRET efficiencies.

Unfolded protein and peptide dynamics investigated with single-molecule FRET and correlation spectroscopy from picoseconds to seconds.

TLDR
The combination of start-stop experiments and classical fluorescence correlation spectroscopy is used to obtain complete intensity auto- and cross-correlation functions from picoseconds to seconds for investigating the dynamics of unfolded proteins and peptides.

Inter-Dye Distance Distributions Studied by a Combination of Single-Molecule FRET-Filtered Lifetime Measurements and a Weighted Accessible Volume (wAV) Algorithm

TLDR
A coarse-grained model is employed to reproduce the experimentally determined inter-dye distance distributions and can easily be extended to intrinsically flexible proteins allowing, under certain conditions, to decouple the macromolecule amplitude of motions from the contribution of the dye linkers.

Single Pair Förster Resonance Energy Transfer: A Versatile Tool To Investigate Protein Conformational Dynamics.

TLDR
Using spFRET on microscopes with different modes of detection, dynamic timescales ranging from nanoseconds to seconds can be quantified and additional computational approaches are required to extract the kinetic rates of these dynamics.
...