Folding funnels

ND Socci, IN Onuchic, PC Wolynes. Protein folding mechanisms and the multi-dimensional folding funnel. Protein Eng 32 136-158, 1998. 

H Nymeyer, AE Garcia, JN Onuchic. Folding funnels and fnrstration in off-lattice mimmalistic protein landscapes. Proc Natl Acad Sci USA 95 5921-5928, 1998. 

PE Leopold, M Montal, JN Onuchic. Protein folding funnels A kinetic approach to the sequence-structure relationship. Pi oc Natl Acad Sci USA 89 8721-8725, 1992. 

Fig. 6. Schematic energy landscape for protein folding (folding funnel). The approximate regions of the energy landscape that correspond to the various partly folded states of apoMb are indicated on the right.

Figure 19.24 A real folding funnel. Refolding chromatography of IGPS (49-252) (indole 3-glycerol phosphate synthase lacking residues 1 -48). Denatured IGPS from an inclusion body was dissolved in 8-M urea and diluted onto a 3-mL column of a GroEL minichaperone (GroEF) that was immobilized on agarose. Ninety-six percent of the protein eluted as fully active material.

Figure 19.16 Cross section through a folding funnel. E corresponds to free energy. [Courtesy of P. G. Wolynes]...

Fiqu re 19.17 Reduction of the folding funnel to a conventional reaction coordinate diagram. This reconciles the classical view of a pathway with the new view of an energy landscape and an ensemble of conformations. [After W. A. Eaton, P. A. Thompson, C. K. Chan, S. Hagen, and J. Hofrichter, Structure 4,1133 (1996).]... 

The initial stages of folding presented a puzzle, the Levinthal paradox, that was solved by the theoreticians using a folding funnel. The final stages of folding present a problem for the experimentalists, especially the biotechnol-... 

Ansari, A., Kuznetsov, S. V., and Shen, Y. (2001). Configurational diffusion down a folding funnel describes the dynamics of DNA hairpins. Proc. Natl. Acad. Sci. USA 98, 7771-7776. 

Leopold, P. E., Motal, M., Onuchic, J. N. Protein folding funnels kinetic pathways through compact computational space Proc. Natl. Acad. Set. USA 1992 89, 8721-8725. 

Onuchic, J. N., Wolynes, P. G., Luthey-Schulten, Z., Socci, N. D. Towards an outline of the topography of a realistic protein folding funnel Proc. Natl. Acad. Sci. USA 1995 92, 3626-3630. 

Ma B, Kumar S, Tsai CJ, Nussinov R. Folding funnels and binding mechanisms. Protein Eng. 1999 12 713-720. 

J.L. Neira and A.R. Fersht. 1999. Exploring the folding funnel of a polypeptide chain by biophysical studies on protein fragments J. Mol. Biol. 285 1309-1333. (PubMed)... 

Shoemaker, B.A., Portman, J.J., Wolynes, P.G. Speeding molecular recognition by using the folding funnel The fly-casting mechanism. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 8868-73. 

Hydrogen bonds and metal coordination bonds have been the mainstay of the supramolecular chemist when it comes to the intentional manipulation of noncovalent interactions. However, nature s examples teach us the power of using weak, non-directional interactions to stabilize the folded state and deepen the folding funnel. Thus, van der Waals and solvophobic interactions are crucial to foldamer design, although they have been scarcely utilized in synthetic systems. In the simplest sense, such input is realized by incorporating amphiphilic character into the chain. 

Plotkin, S. S., Wang, J., and Wolynes, P. G., Statistical mechanics of a correlated energy landscape model for protein folding funnels. 7. Chem. Phys. 106,2932 (1997). 

P. E. Leopold, M. Montal and J. N. Onuchic. Protein folding funnels a kinetic approach to the sequence-structure relationship. Proceedings of the National Academy of Sciences, USA, 89 (1992), 8271 P G. Wolynes, J. N. Onuchic and D. Thirumalai. Navigating the folding routes. Science, 267 (1995), 1619 K. A. Dill and H. S. Chan. From Levinthal to pathways to funnels. Nature Structural Biology, 4 (1997), 10. 

Wolynes, P. G., Folding funnels and energy landscapes of larger proteins within the capillarity approximation. Proc Natl Acad Sci USA, 1997. 94(12) p. 6170-5. 

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