Identifying native-like protein structures with scoring functions based on all-atom ECEPP force fields, implicit solvent models and structure relaxation.

Full 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.

Author information

Author/s: Arnautova, Yelena A (YA); Vorobjev, Yury N (YN); Vila, Jorge A (JA); Scheraga, Harold A (HA);

Affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca New York 14853-1301, USA.

Grants: GM-14312 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Proteins (Proteins), published in United States. (Language: eng)

Reference: 2009-Oct; vol 77 (issue 1) : pp 38-51

Dates: Created 2009/08/24; Completed 2009/10/29;

PMID: 19384995, status: MEDLINE (last retrieval date: 10/29/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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Associated Chemicals: Proteins (0) ; Solvents (0)

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