In this reporting period, papers dealing with the following projects appeared in print: (1) Particle number fluctuations in a membrane channel; (2) Free energy reconstruction from non equilibrium single molecule pulling experiments; (3) Analysis of slow interdomain motion of macromolecules using NMR relaxation data; (4) Long time tails in the kinetics of reversible reactions; (5) Irreversible reactions of Langevin particles. The first three deal directly with the theory required to analyze experiments and the focus will be on these. The first deals with the problem of how to analyse the excess noise in the electric current through membranes to learn about the channel-facilated transport of metabolites. The second solves the important outstanding problem of how to obtain thermodynamic information from micromanipulation of single molecules using lazer tweezers and atomic force microscopes. In such experiments a molecule is forced to undergo conformational changes by pulling on it. Thus the system is driven away from equilibrium. We show how one can extract the energetics of equilibrium conformational changes from repeated force experiments. Thirdly, we show how NMR relaxation data should be interpreted to yield information about the nature of slow interdomain motions of macromolecules. This work focused on calmodulin(CaM) which consists of two domains connected by a flexible helical linker. We were able the determine both the timescale and amplitude of the relative motion of the two domains. This is functionally important because many signalling pathways involve the clamping of a target peptide between the two domains of CaM. It is expected that the method developped in this paper will be widely used.
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