Structured Pathway across the Transition State for Peptide Folding Revealed by Molecular Dynamics Simulations
a) Backbone snapshot of Peptide 1 extracted at the end of the simulation started from the NMR structure. For clarity only the C atoms are shown. b) Contour map of the free energy change, A, as a function of the position in the -R plane (fraction of native contacts, , within the peptide - R parameter). is calculated with respect to the state with the highest probability, i.e., the -hairpin state. Three distinct states can be identified. The states with the two deep minima are the unfolded (U) and folded (F) states and the saddle point corresponds to the single transition state (TS), i.e., the barrier that all molecules must cross if they are to fold to the native state. The F, U and TS states were defined as follows: F comprises all structures populating the basin around the global minimum at = 0.85 and R = 4.95, and with free energy values within 12 kJ/mol from the global minimum; U comprises all structures populating the basin around the local minimum at = 0.10 and R = 2.10, and also with free energy values up to 12 kJ/mol; the structures at the top of the barrier, i.e., not belonging to F or U, were assigned to the TS.