Development of a physics-based force field for the scoring and refinement of protein models

Biophysical Journal
Liliana WroblewskaJeffrey Skolnick

Abstract

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.

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Citations

Jun 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Anna JagielskaJeffrey Skolnick
Jun 8, 2010·Protein Engineering, Design & Selection : PEDS·Yifeng David YangDaisuke Kihara
Jul 31, 2013·PloS One·Debswapna Bhattacharya, Jianlin Cheng
Sep 14, 2013·The Journal of Chemical Physics·W G Noid
Jan 12, 2011·The Journal of Chemical Physics·Marcos R Betancourt
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Jun 14, 2011·Journal of Chemical Theory and Computation·Da-Wei Li, Rafael Brüschweiler

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