Reduced C β statistical potentials can outperform all‐atom potentials in decoy identification

Abstract

We developed a series of statistical potentials to recognize the native protein from decoys, particularly when using only a reduced representation in which each side chain is treated as a single C β atom. Beginning with a highly successful all‐atom statistical potential, the Discrete Optimized Protein Energy function ( DOPE ), we considered the implications of including additional information in the all‐atom statistical potential and subsequently reducing to the C β representation. One of the potentials includes interaction energies conditional on backbone geometries. A second potential separates sequence local from sequence nonlocal interactions and introduces a novel reference state for the sequence local interactions. The resultant potentials perform better than the original DOPE statistical potential in decoy identification. Moreover, even upon passing to a reduced C β representation, these statistical potentials outscore the original (all‐atom) DOPE potential in identifying native states for sets of decoys. Interestingly, the backbone‐dependent statistical potential is shown to retain nearly all of the information content of the all‐atom representation in the C β representation. In addition, these new statistical potentials are combined with existing potentials to model hydrogen bonding, torsion energies, and solvation energies to produce even better performing potentials. The ability of the C β statistical potentials to accurately represent protein interactions bodes well for computational efficiency in protein folding calculations using reduced backbone representations, while the extensions to DOPE illustrate general principles for improving knowledge‐based potentials.