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Identifying native‐like protein structures with scoring functions based on all‐atom ECEPP force fields, implicit solvent models and structure relaxation
Author(s) -
Arnautova Yelena A.,
Vorobjev Yury N.,
Vila Jorge A.,
Scheraga Harold A.
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22414
Subject(s) - force field (fiction) , relaxation (psychology) , mathematics , statistical physics , computer science , thermodynamics , computational chemistry , algorithm , chemistry , physics , artificial intelligence , psychology , social psychology
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 α root‐mean‐square‐deviations below 3.5 Å 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. Proteins 2009. © 2009 Wiley‐Liss, Inc.