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Coupled Folding and Specific Binding: Fishing for Amphiphilicity
Department of Chemical Engineering, The City College of City University of New York, 140th Street and Convent Avenue, Steinman Hall T313, New York, NY 10031, USA
* Author to whom correspondence should be addressed.
Received: 25 January 2011; in revised form: 10 February 2011 / Accepted: 17 February 2011 / Published: 24 February 2011
Abstract: Proteins are uniquely capable of identifying targets with unparalleled selectivity, but, in addition to the precision of the binding phenomenon, nature has the ability to find its targets exceptionally quickly. Transcription factors for instance can bind to a specific sequence of nucleic acids from a soup of similar, but not identical DNA strands, on a timescale of seconds. This is only possible with the enhanced kinetics provided for by a natively disordered structure, where protein folding and binding are cooperative processes. The secondary structures of many proteins are disordered under physiological conditions. Subsequently, the disordered structures fold into ordered structures only when they bind to their specific targets. Induced folding of the protein has two key biological advantages. First, flexible unstructured domains can result in an intrinsic plasticity that allows them to accommodate targets of various size and shape. And, second, the dynamics of this folding process can result in enhanced binding kinetics. Several groups have hypothesized the acceleration of binding kinetics is due to induced folding where a “fly-casting” effect has been shown to break the diffusion-limited rate of binding. This review describes experimental results in rationally designed peptide systems where the folding is coupled to amphiphilicity and biomolecular activity.
Keywords: peptide design; amphiphilic peptide; dynamic folding; binding kinetics
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Jain, V.P.; Tu, R.S. Coupled Folding and Specific Binding: Fishing for Amphiphilicity. Int. J. Mol. Sci. 2011, 12, 1431-1450.
Jain VP, Tu RS. Coupled Folding and Specific Binding: Fishing for Amphiphilicity. International Journal of Molecular Sciences. 2011; 12(3):1431-1450.
Jain, Vikas P.; Tu, Raymond S. 2011. "Coupled Folding and Specific Binding: Fishing for Amphiphilicity." Int. J. Mol. Sci. 12, no. 3: 1431-1450.