Kinetic consistency in the protein folding process

Abstract

The folding process of a small helical protein is simulated with the knowledge-based potential model. Starting from a stretched random conformation, the model peptide chain rapidly collapses to the compact globule state within a 0.1-μs time-scale. Three different types of behaviors are found in the molecular dynamics (MD) trajectories after compaction: folding trajectories along which the chain reaches the native conformation within a μs time-scale; misfolding trajectories along which the chain itinerates globally different conformations from the native conformation; and escaping trajectories along which the chain once takes conformations fairly close to the native conformation but escapes to the other misfolded conformations with μs scale. Consistent growth in both the short-range structure and the long-range structure is an important feature found in the folding trajectories. This kinetic consistency is not fulfilled in the escaping trajectories. A simple spin-glass-like model is developed and it is shown that the design of kinetic connectivity among conformations is important to make the yield of the folding trajectories large.