Physical scoring function based on AMBER force field and Poisson-Boltzmann implicit solvent for protein structure prediction

A well-behaved physics-based all-atom scoring function for protein structure prediction is analyzed with several widely used all-atom decoy sets. The scoring function, termed AMBER/Poisson-Boltzmann (PB), is based on a refined AMBER force field for intramolecular interactions and an efficient PB model for solvation interactions. Testing on the chosen decoy sets shows that the scoring function, which is designed to consider detailed chemical environments, is able to consistently discriminate all 62 native crystal structures after considering the heteroatom groups, disulfide bonds, and crystal packing effects that are not included in the decoy structures. When NMR structures are considered in the testing, the scoring function is able to discriminate 8 out of 10 targets. In the more challenging test of selecting near-native structures, the scoring function also performs very well: for the majority of the targets studied, the scoring function is able to select decoys that are close to the corresponding native structures as evaluated by ranking numbers and backbone Calpha root mean square deviations. Various important components of the scoring function are also studied to understand their discriminative contributions toward the rankings of native and near-native structures. It is found that neither the nonpolar solvation energy as modeled by the surface area model nor a higher protein dielectric constant improves its discriminative power. The terms remaining to be improved are related to 1-4 interactions. The most troublesome term is found to be the large and highly fluctuating 1-4 electrostatics term, not the dihedral-angle term. These data support ongoing efforts in the community to develop protein structure prediction methods with physics-based potentials that are competitive with knowledge-based potentials.