Two-dimensional fluorescence resonance energy transfer as a probe for protein folding: A theoretical study

Abstract

We describe a two-dimensional ͑2D͒, four-color fluorescence resonance energy transfer ͑FRET͒ scheme, in which the conformational dynamics of a protein is followed by simultaneously observing the FRET signal from two different donor-acceptor pairs. For a general class of models that assume Markovian conformational dynamics, we relate the properties of the emission correlation functions to the rates of elementary kinetic steps in the model. We further use a toy folding model that treats proteins as chains with breakable cross-links to examine the relationship between the cooperativity of folding and FRET data and to establish what additional information about the folding dynamics can be gleaned from 2D, as opposed to one-dimensional FRET experiments. We finally discuss the potential advantages of the four-color FRET over the three-color FRET technique.

Exploring the role of internal friction in the dynamics of unfolded proteins using simple polymer models

“…(15) still provides a reasonable measure of a reconfiguration time. 60,61 For RIF or ZIF, Eqs. (14) and (15) can be evaluated analytically.…”

Modeling of Multicolor Single-Molecule Förster Resonance Energy-Transfer Experiments on Protein Folding

“…Nevertheless, it has been found quite successful in predicting characteristic protein states revealed by all-atom simulations, which are essential to compare the multi-and single-color experiments. We assume that three fluorophores are introduced, which is sufficient to perform a multicolor smFRET experiment (although, in principal, two pairs of fluorophores can be considered 47 ). Two fluorophores are placed at the ends of the protein chain, and the third one is positioned at the middle of the chain.…”