Protein Dynamics and the Folding Degree.

The analysis of folding trajectories for proteins is an open challenge. One of the problems is how to describe the amount of folded secondary structure in a protein. We extend the use of Estradas' folding degree (Bioinformatics 2002, 18, 697) for the analysis of the evolution of the folding stage during molecular dynamics (MD) simulation. It is shown that residue contribution to the total folding degree is a predominantly local property, well-defined by the backbone dihedral angles at the given residue, without significant contribution from the backbone conformation of other residues. Moreover, the magnitude of this residue contribution can be quite easily associated with characteristic motifs of secondary protein structures such as the α-helix, β-sheet (hairpin), and so on by means of a Ramachandran-like plot as a function of backbone dihedral angles φ,ψ. Additionally, the understanding of the free energy profile associated with the folding process becomes much simpler. Often a 1D profile is sufficient to locate global minima and the corresponding structure for short peptides.