title: Identifying native-like protein structures with scoring functions based on all-atom ECEPP force fields, implicit solvent models and structure relaxation.
abstract: Availability of energy functions which can discriminate native-like from non-native protein conformations is crucial for theoretical protein structure prediction and refinement of low-resolution protein models. This article reports the results of benchmark tests for scoring functions based on two all-atom ECEPP force fields, that is, ECEPP/3 and ECEPP05, and two implicit solvent models for a large set of protein decoys. The following three scoring functions are considered: (i) ECEPP05 plus a solvent-accessible surface area model with the parameters optimized with a set of protein decoys (ECEPP05/SA); (ii) ECEPP/3 plus the solvent-accessible surface area model of Ooi et al. (Proc Natl Acad Sci USA 1987;84:3086-3090) (ECEPP3/OONS); and (iii) ECEPP05 plus an implicit solvent model based on a solution of the Poisson equation with an optimized Fast Adaptive Multigrid Boundary Element (FAMBEpH) method (ECEPP05/FAMBEpH). Short Monte Carlo-with-Minimization (MCM) simulations, following local energy minimization, are used as a scoring method with ECEPP05/SA and ECEPP3/OONS potentials, whereas energy calculation is used with ECEPP05/FAMBEpH. The performance of each scoring function is evaluated by examining its ability to distinguish between native-like and non-native protein structures. The results of the tests show that the new ECEPP05/SA scoring function represents a significant improvement over the earlier ECEPP3/OONS version of the force field. Thus, it is able to rank native-like structures with C(alpha) root-mean-square-deviations below 3.5 A as lowest-energy conformations for 76% and within the top 10 for 87% of the proteins tested, compared with 69 and 80%, respectively, for ECEPP3/OONS. The use of the FAMBEpH solvation model, which provides a more accurate description of the protein-solvent interactions, improves the discriminative ability of the scoring function to 89%. All failed tests in which the native-like structures cannot be discriminated as those with low energy, are due to omission of protein-protein interactions. The results of this study represent a benchmark in force-field development, and may be useful for evaluation of the performance of different force fields.
authors.affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca New York 14853-1301, USA.
authors.forename: Yelena A
authors.initials: YA
authors.lastname: Arnautova
authors.forename: Yury N
authors.initials: YN
authors.lastname: Vorobjev
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Vila
authors.forename: Harold A
authors.initials: HA
authors.lastname: Scheraga
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D008956:Models, Chemical; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D011506:Proteins; D012997:Solvents