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pubmed-article:19251493pubmed:dateCreated2009-6-5lld:pubmed
pubmed-article:19251493pubmed:abstractTextWe describe and solve a two-state kinetic model for the forced unfolding of proteins. The protein oligomer is modeled as a heterogeneous, freely jointed chain with two possible values of Kuhn length and contour length representing its folded and unfolded configurations. We obtain analytical solutions for the force-extension response of the protein oligomer for different types of loading conditions. We fit the analytical solutions for constant-velocity pulling to the force-extension data for ubiquitin and fibrinogen and obtain model parameters, such as Kuhn lengths and kinetic coefficients, for both proteins. We then predict their response under a linearly increasing force and find that our solutions for ubiquitin are consistent with a different set of experiments. Our calculations suggest that the refolding rate of proteins at low forces is several orders larger than the unfolding rate, and neglecting it can lead to lower predictions for the unfolding force, especially at high stretching velocities. By accounting for the refolding of proteins we obtain a critical force below which equilibrium is biased in favor of the folded state. Our calculations also suggest new methods to determine the distance of the transition state from the energy wells representing the folded and unfolded states of a protein.lld:pubmed
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pubmed-article:19251493pubmed:authorpubmed-author:PurohitPrasha...lld:pubmed
pubmed-article:19251493pubmed:authorpubmed-author:SuTianxiangTlld:pubmed
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pubmed-article:19251493pubmed:year2009lld:pubmed
pubmed-article:19251493pubmed:articleTitleMechanics of forced unfolding of proteins.lld:pubmed
pubmed-article:19251493pubmed:affiliationDepartment of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, Philadelphia, 19104, USA.lld:pubmed
pubmed-article:19251493pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:19251493pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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