Utilizing the information content in two-state trajectories

The signal from many single-molecule experiments monitoring molecular processes, such as enzyme turnover by means of fluorescence and opening and closing of ion channel through the flux of ions, consists of a time series of stochastic "on" and "off" (or open and closed) periods, termed a two-state trajectory. This signal reflects the dynamics in the underlying multisubstate on-off kinetic scheme (KS) of the process. The determination of the underlying KS is difficult and sometimes even impossible because of the loss of information in the mapping of the multidimensional KS onto two dimensions. Here we introduce a previously undescribed procedure that efficiently and optimally relates the signal to all equivalent underlying KS. This procedure partitions the space of KS into canonical (unique) forms that can handle any KS and obtains the topology and other details of the canonical form from the data without the need for fitting. Also established are relationships between the data and the topology of the canonical form to the on-off connectivity of a KS. The suggested canonical forms constitute a powerful tool in discriminating between KS. Based on our approach, the upper bound on the information content in two-state trajectories is determined.