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Unique mechanisms from finite two-state trajectories

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 نشر من قبل Ophir Flomenbom
 تاريخ النشر 2007
  مجال البحث علم الأحياء فيزياء
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Single molecule data made of on and off events are ubiquitous. Famous examples include enzyme turnover, probed via fluorescence, and opening and closing of ion-channel, probed via the flux of ions. The data reflects the dynamics in the underlying multi-substate on-off kinetic scheme (KS) of the process, but the determination of the underlying KS is difficult, and sometimes even impossible, due to the loss of information in the mapping of the mutli-dimensional KS onto two dimensions. A way to deal with this problem considers canonical (unique) forms. (Unique canonical form is constructed from an infinitely long trajectory, but many KSs.) Here we introduce canonical forms of reduced dimensions that can handle any KS (i.e. also KSs with symmetry and irreversible transitions). We give the mapping of KSs into reduced dimensions forms, which is based on topology of KSs, and the tools for extracting the reduced dimensions form from finite data. The canonical forms of reduced dimensions constitute a powerful tool in discriminating between KSs.



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The signal from many single molecule experiments monitoring molecular processes, such as enzyme turnover via fluorescence and opening and closing of ion channel via the flux of ions, consists of a time series of stochastic on and off (or open and clo sed) periods, termed a two-state trajectory. This signal reflects the dynamics in the underlying multi-substate on-off kinetic scheme (KS) of the process. The determination of the underlying KS is difficult and sometimes even impossible due to the loss of information in the mapping of the mutli dimensional KS onto two dimensions. Here we introduce a new procedure that efficiently and optimally relates the signal to all equivalent underlying KSs. This procedure partitions the space of KSs 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 KSs. Based on our approach, the upper bound on the information content in two state trajectories is determined.
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