  Detecting conformational transitions in molecular systems is key to
understanding biological processes. Here, we investigate the force variance in
single-molecule pulling experiments as an indicator of molecular folding
transitions. We consider cases where Brownian force fluctuations are large,
masking the force rips and jumps characteristic of conformational transitions.
We compare unfolding and folding data for DNA hairpin systems of loop sizes
4,8, and 20 and the 110 amino acids protein barnase, finding conditions that
facilitate the detection of folding events at low forces where the
signal-to-noise ratio is low. In particular, we discuss the role of temperature
as a useful parameter to improve the detection of folding transitions in
entropically driven processes where folding forces are temperature-independent.
The force variance approach might be extended to detect the elusive
intermediate states in RNA and protein folding.
