A minima hopping study of all-atom protein folding and structure prediction.

The minima hopping algorithm (MHOP) to find global minima on potential energy surfaces is used for protein structure prediction. The energy surface of the protein is represented with an all-atom OPLS force field and an implicit free energy solvation term. The system we studied here is the small 10-residue beta-hairpin mini-protein, chignolin. Starting from a completely extended structure, we found minima with <0.5 A rms coordinate deviation from the geometry-optimized native experimental conformation. A few lowest-energy conformations were used for the calculation of NMR-restraint violations and chemical shifts, and the local minima found during each run leading to the global minimum were connected to trace out a search pathway of the folding process.