The interplay between structure-search of the native structure and desolvation in protein folding has been explored using a minimalist model. These results support a folding mechanism where most of the structural formation of the protein is achieved before water is expelled from the hydrophobic core. This view integrates water expulsion effects into the funnel energy landscape theory of protein...

The interplay between structure-search of the native structure and desolvation in protein folding has been explored using a minimalist model. These results support a folding mechanism where most of the structural formation of the protein is achieved before water is expelled from the hydrophobic core. This view integrates water expulsion effects into the funnel energy landscape theory of protein...

Do stable intermediates form very early in the protein folding process? New results and a quantity of literature that bear on this issue are examined here. Results available provide little support for early intermediate accumulation before an initial search-dependent nucleation barrier.

A high resolution reduced model of proteins is used in Monte Carlo dynamics studies of the folding mechanism of a small globular protein, the B1 immunoglobulin-binding domain of streptococcal protein G. It is shown that in order to reproduce the physics of the folding transition, the united atom based model requires a set of knowledge-based potentials mimicking the short-range conformational pr...

The GroE chaperones of Escherichia coli promote the folding of other proteins under conditions where no spontaneous folding occurs. One requirement for this reaction is the trapping of the nonnative protein inside the chaperone complex. Encapsulation may be important to prevent unfavorable intermolecular interactions during folding. We show here that, especially for oligomeric proteins, the tim...

We use infrared spectroscopy to study the evolution of protein folding intermediate structures on arbitrarily slow time scales by rapidly quenching thermally unfolded hen egg white lysozyme in a glassy matrix, followed by reheating of the protein to refold; upon comparison with differential scanning calorimetric experiments, low-temperature structural changes that precede the formation of energ...

The physical basis of two-state-like folding transitions and the tremendous diversity in folding rates is elucidated by directly simulating the folding kinetics of 52 representative proteins. Relative to the results from a common modeling approach, the diversity of the simulated folding rates can be increased from ~10(2.1) to the experimental ~10(6.0) by a modest decrease in the spatial range o...

We consider a simplified model of protein folding, with binary degrees of freedom, whose equilibrium thermodynamics is exactly solvable. Based on this exact solution, the kinetics is studied in the framework of a local equilibrium approach, for which we prove that (i) the free energy decreases with time, (ii) the exact equilibrium is recovered in the infinite time limit, and (iii) the equilibra...

Many small, monomeric proteins fold with simple two-state kinetics and show wide variation in folding rates, from microseconds to seconds. Thus, stable intermediates are not a prerequisite for the fast, efficient folding of proteins and may in fact be kinetic traps and slow the folding process. Using recent studies, can we begin to search for trends which may lead to a better understanding of t...

In an attempt to explore the understanding of protein folding mechanism, various models have been proposed in the literature. Advances in recent experimental and computational techniques rationalized our understanding on some of the fundamental features of the protein folding pathways. The goal of this review is to revisit the various models and outline the essential aspects of the folding reac...