A protein model with the pairwise interaction energies varying as the local environment changes, i.e., including some kind of collective effect between the contacts, is proposed. Lattice Monte Carlo simulations on the thermodynamical characteristics and free energy profile show a well-defined two-state behavior and cooperativity of folding for such a model. As a comparison, related simulations ...

Proteins fold using a two-state or multi-state kinetic mechanisms, but up to now there is not a first-principle model to explain this different behavior. We exploit the network properties of protein structures by introducing novel observables to address the problem of classifying the different types of folding kinetics. These observables display a plain physical meaning, in terms of vibrational...

We present a solvable model that predicts the folding kinetics of two-state proteins from their native structures. The model is based on conditional chain entropies. It assumes that folding processes are dominated by small-loop closure events that can be inferred from native structures. For CI2, the src SH3 domain, TNfn3, and protein L, the model reproduces two-state kinetics, and it predicts w...

T he study of the folding of membrane proteins has lagged far behind that of small soluble proteins—yet proteins that reside within biological membranes account for approximately a third of all proteomes. The article by Huysmans et al. in this issue of PNAS (1) represents a breakthrough by reporting a comprehensive φ-value analysis of the folding of a membrane protein (i.e., PagP) into a lipid ...

Most secreted bacterial proteases, including -lytic protease ( LP), are synthesized with covalently attached pro regions necessary for their folding. The LP folding landscape revealed that its pro region, a potent folding catalyst, is required to circumvent an extremely large folding free energy of activation that appears to be a consequence of its unique unfolding transition. Remarkably, the L...

Folding channels and free-energy landscapes of hydrophobic-polar heteropolymers are discussed on the basis of a minimalistic off-lattice coarse-grained model. We investigate how rearrangements of hydrophobic and polar monomers in a heteropolymer sequence lead to completely different folding behaviors. Studying three exemplified sequences with the same content of hydrophobic and polar residues, ...

Folding channels and free-energy landscapes of hydrophobic-polar heteropolymers are discussed on the basis of a minimalistic off-lattice coarse-grained model. We investigate how rearrangements of hydrophobic and polar monomers in a heteropolymer sequence lead to completely different folding behaviors. Studying three exemplified sequences with the same content of hydrophobic and polar residues, ...

5. Thermodynamics and kinetics of protein folding 234 5.1 A protein Hamiltonian with cooperative interactions 234 5.2 Variance of native contact energies 235 5.3 Thermodynamics of protein folding 236 5.4 Free-energy surfaces and dynamics for a Hamiltonian with pair-wise interactions 240 5.5 The effects of cooperativity on folding 242 5.6 Transition-state drift 242 5.7 Phase diagram for a model ...

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...

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...