Strain-dependent fluorescence correlation spectroscopy: Proposing a new measurement for conformational fluctuations of biological macromolecules

We have proposed a measurement in which a single protein or nucleic acid molecule is held by an externally applied tension in a partially folded intermediate state. In this state it could be possible to observe the dynamics of conformational changes that would be obscured by conformational cooperativity in conventional experiments, We have presented a simple model that illustrates how this approach might work to reveal states, which could not readily be observed in the absence of the applied force. This measurement approach is applicable to any macromolecular system and could be especially useful in analyzing the processes that dominate protein folding kinetic studies of which began three decades ago [4.30].