Protein folding kinetics in the dense phase

The standard theoretical approach to the protein folding problem uses the thermodynamic hypothesis to justify the assumption that proteins fold to the global minimum free energy. The authors present simple arguments suggesting that minimization of energy during folding is unnecessary for the phenomena observed. In place of the energy minimization strategies, they describe a tractable kinetic model of folding that permits a systematic survey of the dynamical properties of the collapsed proteins. It is demonstrated that the first-order kinetic approximation for interconversion between geometrically similar compact structures is valid for the limiting examples of homopolymers. Rate constants for structural interconversion are calculated using a stochastic equation and are shown to be consistent with rates determined from Monte Carlo kinetics simulations.