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Though smFRET was demonstrated for the first time by Ha et al., in 1996 by obtaining simultaneous dual color images and emission spectra from donor and acceptor fluorophores linked by a short DNA molecule (Ha et al., 1996), the first actual application of this tool in analysis of IDPs was reported in 2007 by Mukhopadhyay et al., who demonstrated that the natively unfolded yeast prion protein adopts an ensemble of collapsed and rapidly fluctuating structures (Mukhopadhyay et al., 2007)