Folding nucleus

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

El Shakhnovich. Folding nucleus Specific or multiple Insights from lattice models and experiments. Folding Des 3 R108-R111, 1998. 

The Fold Nucleus is Formed From Both the FCC-Melt and ECSC-Melt... 

This indicates that fixing of the torsion about the phenylacetylene bond leads to a AAG(CH3CN) of 1.2 kcal mol very close to the expected stabilization for AGnuc upon fixing of one torsion. This demonstrates that stabilization of the folding nucleus through supramolecular interactions leads to the stabilization of the folded-state structure. 

Figure 19.10 A critical number of interactions are required to form a folding nucleus. The figure is oversimplified in that the enthalpy is shown to decrease throughout folding. In practicej there will be some gain in enthalpy as the transition state is reached because of the loss of energy of solvation and the incomplete formation of the interactions present in the native state.

By analyzing experimental data Akmal and Munoz [18] conclude that the top of the free energy barrier is reached when the protein in its search for the native state reaches a critical native density , i.e. is close enough to the native state to expel the interstitial water molecules and form a folding nucleus. At that point the stabilization energy starts to overcome the decrease of conformational entropy. In addition, the expelled interstitial solvent gains translational entropy as well [19]. 

Mechanism in Protein Folding Evidence for the Non-uniqueness of the Folding Nucleus. 

Identifying the Protein Folding Nucleus Using Molecular Dynamics. 

S. Honda, N. Kobayashi, and E. Munekata, Theormodynamics of a P-hairpin structure Evidence for cooperative formation of folding nucleus. J. Mol. Biol. 295(2), 269-278 (2000). 

Predictions from these model studies match well with results on experimental protein folding studies of some real proteins (Ortiz and Skolnick, unpublished). Indeed, when a similar procedure is employed on real proteins for which experimental data are available, there is a substantial overlap between the folding nucleus found experimentally and the folding nucleus predicted from the multivariate analysis of multiple sequence alignments. 

Thus, once the seeds are expanded, we speculate that a substantial proportion of the real folding nucleus of the protein is used as a restraint in the MONSSTER simulations. 

O. B. Ptitsyn and K. L. Ting,/. Mol. Biol., 291, 671 (1999). Non-Functional Conserved Residues in Globins and their Possible Role as a Folding Nucleus. 

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