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

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.

SUBMITTER: Wroblewska L

PROVIDER: S-EPMC2275715 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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

Wroblewska Liliana L Jagielska Anna A Skolnick Jeffrey J

Biophysical journal 20080104 8

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 ...[more]

PMID: 18178653

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Project description:We employ the popular all-atom optimized potential for liquid simulations, OPLSAA, force-field to model 17 different alcohols in the liquid state. Using the standard simulation protocol for few hundred nanosecond time periods, we find that 1-octanol, 1-nonanol, and 1-decanol undergo spontaneous transition to a crystalline state at temperatures which are 35-55 K higher than the experimental melting temperatures. Nevertheless, the crystal structures obtained from the simulations are very similar to those determined by X-ray powder diffraction data for several n-alcohols. Although some degree of deviations from the experimental freezing points are to be expected, for 1-nonanol and 1-decanol, the elevation of the freezing temperature warrants special attention because at room temperature, these alcohols are liquids; however, if simulated by the OPLSAA force-field, they will crystallize. This behavior is likely a consequence of exaggerated attractive interactions between the alkane chains of the alcohols. To circumvent this problem, we combined the OPLSAA model with the L-OPLS force-field. We adopted the L-OPLS parameters to model the hydrocarbon tail of the alcohols, whereas the hydroxyl head group remained as in the original OPLSAA force-field. The resulting alcohols stayed in the liquid state at temperatures above their experimental melting points, thus, resolving the enhanced freezing observed with the OPLSAA force-field. In fact, the mixed-model alcohols did not exhibit any spontaneous freezing even at temperatures much lower than the experimental values. However, a series of simulations in which these mixed-OPLSAA alcohols started from a coexistence configuration of the liquid and solid phases resulted in freezing transitions at temperatures 14-25 K lower than the experimental values, confirming the validity of the proposed model. For all of the other alcohols, the mixed model yields results very similar to the OPLSAA force-field and is in good agreement with the experimental data. Thus, for simulating alcohols in the liquid phase, the mixed-OPLSAA model is necessary for large (7 carbons and above) hydrocarbon chains.

Dataset Information

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

Publications

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

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