Noise reduction in single-molecule fluorescence trajectories of folding proteins

A method for noise reduction in stochastic trajectories of single molecules is described. The method generalizes a nonlinear filtration technique developed by Chung and Kennedy for single-channel recording [J. Neurosci. Meth. 40 (1991) 71] and applies it to the case of two correlated trajectories, as in a fluorescence resonance energy transfer experiment. Thus it is particularly suitable for single-molecule studies of protein folding. It is shown that the nonlinear filter facilitates the detection of various intermediate conformational states in a noisy trajectory, and can provide better estimates for the temporal positions of jumps between states and dwell times than a standard low-pass filter. It is finally suggested that the filter can also be of use for directly resolving molecular motion through the transition state region on the folding energy landscape. (C) 2004 Elsevier B.V. All rights reserved.