BIOPHYSICAL THEORY AND MODELING |
Towards resolution of ambiguity for the unfolded state
Gregory Beaucage 1*
1 University of Cincinnati
* To whom correspondence should be addressed. E-mail: gbeaucage{at}gmail.com.
Submitted on September 12, 2007
Revised on October 5, 2007
Accepted on 9 January 2008
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Abstract |
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The unfolded states in proteins and nucleic acids remain weakly understood despite their importance to understanding folding processes; misfolding diseases (Parkinson's & Alzheimer's); natively unfolded proteins (as many as 30% of eukaryotic proteins [Fink, 2005]); and to the study of ribozymes. Research has been hindered by the inability to quantify the residual (native) structure present in an unfolded protein or nucleic acid. Here, a scaling model is proposed to quantify the molar degree of folding and the unfolded state. The model takes a global view of protein structure and can be applied to a number of analytic methods and to simulations. Three examples are given of application to small-angle scattering from pressure induced unfolding of SNase, from acid unfolded Cyt c and from folding of Azoarcus ribozyme. These examples quantitatively show 3 characteristic unfolded states for proteins, the statistical nature of a protein folding pathway and the relationship between extent of folding and chain size during folding for charge driven folding in RNA.
Key Words:
Cytochrome c, Fractal Dimension, Protein Folding, RNA Folding, Ribozyme, Staphylococcal nuclease
