Browsing by Author "Burger, Anat"

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    Discrete Kinetic Models from Funneled Energy Landscape Simulations
    (Public Library of Science, 2012) Schafer, Nicholas P.; Hoffman, Ryan M.B.; Burger, Anat; Craig, Patricio O.; Komives, Elizabeth A.
    A general method for facilitating the interpretation of computer simulations of protein folding with minimally frustrated energy landscapes is detailed and applied to a designed ankyrin repeat protein (4ANK). In the method, groups of residues are assigned to foldons and these foldons are used to map the conformational space of the protein onto a set of discrete macrobasins. The free energies of the individual macrobasins are then calculated, informing practical kinetic analysis. Two simple assumptions about the universality of the rate for downhill transitions between macrobasins and the natural local connectivity between macrobasins lead to a scheme for predicting overall folding and unfolding rates, generating chevron plots under varying thermodynamic conditions, and inferring dominant kinetic folding pathways. To illustrate the approach, free energies of macrobasins were calculated from biased simulations of a non-additive structure-based model using two structurally motivated foldon definitions at the full and half ankyrin repeat resolutions. The calculated chevrons have features consistent with those measured in stopped flow chemical denaturation experiments. The dominant inferred folding pathway has an “inside-out”, nucleation-propagation like character.
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    Influence of decoys on the noise and dynamics of gene expression
    (American Physical Society, 2012) Burger, Anat; Walczak, Aleksandra M.; Wolynes, Peter G.; Center for Theoretical Biological Physics
    Many transcription factors bind to DNA with a remarkable lack of specificity, so that regulatory binding sites compete with an enormous number of nonregulatory “decoy” sites. For an autoregulated gene, we show decoy sites decrease noise in the number of unbound proteins to a Poisson limit that results from binding and unbinding. This noise buffering is optimized for a given protein concentration when decoys have a 1/2 probability of being occupied. Decoys linearly increase the time to approach steady state and exponentially increase the time to switch epigenetically between bistable states.