Statistical approaches for probing single-molecule dynamics photon-by-photon

The recently developed photon-by-photon approach [H. Yang, X.S. Xie, J. Chem. Phys., 2002 (in press)] for single-molecule fluorescence experiments allows measurements of conformational fluctuation with time resolution on a vast range of time scales. In that method, each photon represents a data point, thereby affording better statistics. Here, we utilize the information carried by each detected photon to better differentiate theoretical models for the underlying dynamical processes - including two- and three-state models, and a diffusive model. We introduce a three-time correlation analysis, which is based on time series analyses, and the Kullback-Liebler distance, which is based on information theory principles [Elements of Information Theory, Wiley, New York, 1991]. The feasibility of and general procedures for applying these methods to single-molecule experiments are examined via computer simulations.