Lessons from application of the UNRES force field to predictions of structures of CASP10 targets

With the example of the coarse-grained United Residue model of polypeptide chains, this paper demonstrates that the physics-based approach for protein-structure prediction can lead to exceptionally good results when correct domain packing is an issue, even for a highly homologous target. The reason for this is probably that emphasis is placed on energetically favorable residue–residue interactions, including those with residues in relatively flexible linker regions; these regions are usually very different in the target compared with those of proteins in the databases used for template-based modeling. The results suggest that a combination of bioinformatics and a physics-based approach could result in a major increase in the prediction capacity of existing approaches.