Development of a Physics-Based Force Field
for the Scoring and Refinement of Protein Models
Liliana Wroblewska 1, Anna Jagielska 1 and Jeffrey Skolnick 1*
1 Georgia Tech
* To whom correspondence should be addressed. E-mail: skolnick{at}gatech.edu.
Submitted on September 20, 2007
Revised on October 14, 2007
Accepted on 7 December 2007
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Abstract |
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The minimal requirements of a physics based potential that can refine protein structures is the existence of a correlation between the energy with native similarity and the scoring of the native structure as being 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.
Key Words:
Amber potential, all-atom force fields, global optimization, protein structure refinement, scoring of protein decoys
