There are many unresolved questions regarding the role of water in protein folding. Does water merely induce hydrophobic forces, or does the discrete nature of water play a structural role in folding? Are the nonadditive aspects of water important in determining the folding mechanism? To help to address these questions, we have performed simulations of the folding of a model protein (BBA5) in e...

Chevron rollovers of some proteins imply that their logarithmic folding rates are nonlinear in native stability. This is predicted by lattice and continuum Gō models to arise from diminished accessibilities of the ground state from transiently populated compact conformations under strongly native conditions. Despite these models' native-centric interactions, the slowdown is due partly to kineti...

The folding reactions of some small proteins show clear evidence of a hierarchic process, whereas others, lacking detectable intermediates, do not. Evidence from folding intermediates and transition states suggests that folding begins locally, and that the formation of native secondary structure precedes the formation of tertiary interactions, not the reverse. Some notable examples in the liter...

BACKGROUND The role of intermediates in protein folding has been a matter of great controversy. Although it was widely believed that intermediates play a key role in minimizing the search problem associated with the Levinthal paradox, experimental evidence has been accumulating that small proteins fold fast without any detectable intermediates. RESULTS We study the thermodynamics and kinetics...

Using a statistical mechanical treatment, we study RNA folding energy landscapes. We first validate the theory by showing that, for the RNA molecules we tested having only secondary structures, this treatment (i) predicts about the same native structures as the Zuker method, and (ii) qualitatively predicts the melting curve peaks and shoulders seen in experiments. We then predict thermodynamic ...

A recent proteome analysis of protein folding inside cells of Escherichia coli predicts that only 84 of the approximately 2400 cytosolic proteins expressed in minimal media depend absolutely on the GroEL/GroES chaperone system to avoid aggregation. These proteins are enriched in alpha/beta domains and 13 are essential for growth.

The hydrophobic effect is considered the main driving force for protein folding and plays an important role in the stability of those biomolecules. Cold denaturation, where the native state of the protein loses its stability upon cooling, is also attributed to this effect. It is therefore not surprising that a lot of effort has been spent in understanding this phenomenon. Despite these efforts,...

In a recent issue of Science, Greenleaf et al. (2008) report single-molecule force measurements to explore the sequential folding landscape of an adenine riboswitch aptamer domain. This study provides an exceptionally quantitative view of how an RNA molecule folds.

The translocation of structured RNA or DNA molecules through narrow pores necessitates the opening of all base pairs. Here, we study the interplay between the dynamics of translocation and base pairing theoretically, using kinetic Monte Carlo simulations and analytical methods. We find that the transient formation of base pairs that do not occur in the ground state can significantly speed up tr...

Theory indicates that at least some proteins will undergo a rapid and unimpeded collapse, like a disorganized hydrophobic chain, prior to folding. Yet experiments continue to find signs of an organized, or barrier-limited, collapse in even the fastest (approximately mus) folding proteins. Does the kinetic barrier represent a signature of the equilibrium "foldability" of these molecules? We have...