Predictive and reproducible de novo all-atom folding of a β-hairpin loop in an improved free-energy forcefield

We have recently improved our free- energy forcefield for all- atom de novo protein folding to address the folding of proteins with beta- sheet secondary structure. The folding of beta strands is nevertheless more difficult than that of helical proteins, because of non- local interactions between regions of the protein chain that are not consecutive in the amino acid sequence. Here we use a greedy version of the basin- hopping technique with our free- energy forcefield PFF02 to reproducibly and predictively fold the structure of a beta- hairpin loop. The lowest energy structure found in the simulation has a backbone root mean square deviation of only 2.62 Alpha to the native conformation. The side- chain alignment is also correctly predicted, as are four of the five backbone hydrogen bonds found in the native structure.