A discriminative Ramachandran potential of mean force aimed at minimizing secondary structure bias

We introduce PMF*, a novel potential of mean force (PMF) for the Ramachandran ϕ/Ψ dihedral plot of the 20 standard amino acids and assess its relevance to the conformation of polypeptides by scoring structures in the protein data bank and decoy datasets. The new energy function is a linear combination of the conventional, unreferenced PMF and the ΔPMF relative to the free energy of all amino acids in the parameterization set of structures, effectively removing their respective biases toward α-helix and β-strand. It is shown that low-resolution crystal structures, NMR structures, and theoretical models have on average significantly higher energies than high-resolution crystal structures; also PMF* is more discriminative for structure quality than the individual PMF and ΔPMF energy functions. PMF* may be well suited for use as a restraint energy term in the refinement of experimental structures and theoretical models.