This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.107.121947v1 94/8/3227    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wroblewska, L. Articles by Skolnick, J. PubMed PubMed Citation Articles by Wroblewska, L. Articles by Skolnick, J.

Development of a Physics-Based Force Field for the Scoring and Refinement of Protein Models

Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30318

Correspondence: Address reprint requests to Jeffrey Skolnick, Tel.: 404-407-8975; Fax: 404-385-7478; E-mail: skolnick{at}gatech.edu.

The minimal requirements of a physics-based potential that can refine protein structures are the existence of a correlation between the energy with native similarity and the scoring of the native structure as the lowest in energy. To develop such a force field, the relative weights of the Amber ff03 all-atom potential supplemented by an explicit hydrogen-bond potential were adjusted by global optimization of energetic and structural criteria for a large set of protein decoys generated for a set of 58 nonhomologous proteins. The average correlation coefficient of the energy with TM-score significantly improved from 0.25 for the original ff03 potential to 0.65 for the optimized force field. The fraction of proteins for which the native structure had lowest energy increased from 0.22 to 0.90. Moreover, use of an explicit hydrogen-bond potential improves scoring performance of the force field. Promising preliminary results were obtained in applying the optimized potentials to refine protein decoys using only an energy criterion to choose the best decoy among sampled structures. For a set of seven proteins, 63% of the decoys improve, 18% get worse, and 19% are not changed.