Resolution of the unfolded state.

The unfolded states in proteins and nucleic acids remain weakly understood despite their importance to protein folding; misfolding diseases (Parkinson's {\&} Alzheimer's); natively unfolded proteins ($\sim $ 30{\%} of eukaryotic proteins); and to understanding 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 \textit{degree of folding} and the unfolded state (Beaucage, 2004, 2007). 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 (Panick, 1998), from acid unfolded Cyt c (Kataoka, 1993) and from folding of \textit{Azoarcus} ribozyme (Perez-Salas, 2004). These examples quantitatively show 3 characteristic unfolded states for proteins, the statistical nature of a folding pathway and the relationship between extent of folding and chain size during folding for charge driven folding in RNA. Beaucage, G., \textit{Biophys. J.}, in press (2007). Beaucage, G., \textit{Phys. Rev. E}. \textbf{70}, 031401 (2004). Kataoka, M., Y. Hagihara, K. Mihara, Y. Goto \textit{J. Mol. Biol.} \textbf{229}, 591 (1993). Panick, G., R. Malessa, R. Winter, G. Rapp, K. J. Frye, C. A. Royer \textit{J. Mol. Biol.} \textbf{275}, 389 (1998). Perez-Salas U. A., P. Rangan, S. Krueger, R. M. Briber, D. Thirumalai, S. A. Woodson, \textit{Biochemistry} \textbf{43} 1746 (2004).