Unraveling multi-state molecular dynamics in single-molecule FRET experiments. II. Quantitative analysis of multi-state kinetic networks.

@article{Opanasyuk2022UnravelingMM,
  title={Unraveling multi-state molecular dynamics in single-molecule FRET experiments. II. Quantitative analysis of multi-state kinetic networks.},
  author={O. A. Opanasyuk and Anders Barth 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={157 3},
  pages={
          031501
        }
}
Single-molecule Förster Resonance Energy Transfer (smFRET) experiments are ideally suited to resolve the structural dynamics of biomolecules. A significant challenge to date is capturing and quantifying the exchange between multiple conformational states, mainly when these dynamics occur on the sub-millisecond timescale. Many methods for quantitative analysis are challenged if more than two states are involved, and the appropriate choice of the number of states in the kinetic network is… 
3 Citations

Figures and Tables from this paper

A blind benchmark of analysis tools to infer kinetic rate constants from single-molecule FRET trajectories

TLDR
A blind benchmark study assessing eleven analysis tools used to infer kinetic rate constants from smFRET trajectories, testing on simulated and experimental data and identifying key targets for future developments to advance the understanding of biomolecular dynamics.

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 44 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.

Two-dimensional fluorescence lifetime correlation spectroscopy. 1. Principle.

TLDR
This work develops a new method that combines FCS and time-correlated single photon counting (TCPSC) to extract unambiguous information about equilibrium dynamics of complex molecular systems and performs a kinetic Monte Carlo simulation of a TCPSC-FCS experiment as a proof-of-principle example.

Photon-by-Photon Hidden Markov Model Analysis for Microsecond Single-Molecule FRET Kinetics.

TLDR
H2MM, a maximum likelihood estimation algorithm for photon-by-photon analysis of single-molecule fluorescence resonance energy transfer (FRET) experiments, is introduced and paves the way for the broad application ofsingle-molescular fluorescence to study ultrafast functional dynamics of biomolecules.

Characterizing single-molecule FRET dynamics with probability distribution analysis.

TLDR
A generalized PDA method is used to predict the shapes of FRET histograms for molecules interconverting dynamically between multiple states, and is expected to be useful in extracting rates from processes exhibiting dynamic FRET, and in hypothesis-testing models of conformational dynamics against experimental data.

Measuring conformational dynamics: a new FCS-FRET approach.

TLDR
This work presents a new approach based on the simultaneous analysis of the auto- and cross-correlation functions of the intensities measured in two independent detectors for a donor-acceptor labeled biomolecule, and shows that the same kinetic information can be obtained from a single experiment with a double-labeled biomolecules.

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.

Detecting intramolecular dynamics and multiple Förster resonance energy transfer states by fluorescence correlation spectroscopy.

TLDR
The reliability of the method for isolating intramolecular dynamics from other dynamic processes on the microsecond time scale is demonstrated and the sensitivity of the initial amplitudes of the FCS auto- and cross-correlation functions to the presence of multiple FRET states, static or dynamic is shown.

Combining Graphical and Analytical Methods with Molecular Simulations To Analyze Time-Resolved FRET Measurements of Labeled Macromolecules Accurately

TLDR
The developed fast simulation methods allow us to incorporate structural information in the decay analysis for heterogeneous cases by relating dye states with protein conformations to pave the way for fluorescence and FRET-based dynamic structural biology.