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COFFDROP: A Coarse-Grained Nonbonded Force Field for Proteins Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of Amino Acids.

Andrews CT, Elcock AH - J Chem Theory Comput (2014)

Bottom Line: In a first test of the force field, it was used to predict the clustering behavior of concentrated amino acid solutions; the predictions were directly compared with the results of corresponding all-atom explicit-solvent MD simulations and found to be in excellent agreement.The anomalously strong intermolecular interactions seen in the MD study were reproduced in the COFFDROP simulations; a simple scaling of COFFDROP's nonbonded parameters, however, produced results in better accordance with experiment.Overall, our results suggest that potential functions derived from simulations of pairwise amino acid interactions might be of quite broad applicability, with COFFDROP likely to be especially useful for modeling unfolded or intrinsically disordered proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States.

ABSTRACT
We describe the derivation of a set of bonded and nonbonded coarse-grained (CG) potential functions for use in implicit-solvent Brownian dynamics (BD) simulations of proteins derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acids. Bonded potential functions were derived from 1 μs MD simulations of each of the 20 canonical amino acids, with histidine modeled in both its protonated and neutral forms; nonbonded potential functions were derived from 1 μs MD simulations of every possible pairing of the amino acids (231 different systems). The angle and dihedral probability distributions and radial distribution functions sampled during MD were used to optimize a set of CG potential functions through use of the iterative Boltzmann inversion (IBI) method. The optimized set of potential functions-which we term COFFDROP (COarse-grained Force Field for Dynamic Representation Of Proteins)-quantitatively reproduced all of the "target" MD distributions. In a first test of the force field, it was used to predict the clustering behavior of concentrated amino acid solutions; the predictions were directly compared with the results of corresponding all-atom explicit-solvent MD simulations and found to be in excellent agreement. In a second test, BD simulations of the small protein villin headpiece were carried out at concentrations that have recently been studied in all-atom explicit-solvent MD simulations by Petrov and Zagrovic (PLoS Comput. Biol. 2014, 5, e1003638). The anomalously strong intermolecular interactions seen in the MD study were reproduced in the COFFDROP simulations; a simple scaling of COFFDROP's nonbonded parameters, however, produced results in better accordance with experiment. Overall, our results suggest that potential functions derived from simulations of pairwise amino acid interactions might be of quite broad applicability, with COFFDROP likely to be especially useful for modeling unfolded or intrinsically disordered proteins.

No MeSH data available.


Related in: MedlinePlus

Example nonbonded potential functions. (A) Plot comparing the Ace–Acenonbonded potential function of the val–val system obtainedfrom IBI (blue) with that obtained from noniterative Boltzmann inversion(red) of the MD g(r) function. (B)Same as A but for the Cα–Cα interaction; (C) sameas A but for the Cβ–Cβ interaction. (D) Plot comparingthe Ace–Ace g(r) of the val-valsystem obtained from MD (black circles) with that obtained from BDusing COFFDROP (blue line). (E) Same as D but for for the Cα–Cαinteraction; (F) same as D but for the Cβ–Cβ interaction.
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fig5: Example nonbonded potential functions. (A) Plot comparing the Ace–Acenonbonded potential function of the val–val system obtainedfrom IBI (blue) with that obtained from noniterative Boltzmann inversion(red) of the MD g(r) function. (B)Same as A but for the Cα–Cα interaction; (C) sameas A but for the Cβ–Cβ interaction. (D) Plot comparingthe Ace–Ace g(r) of the val-valsystem obtained from MD (black circles) with that obtained from BDusing COFFDROP (blue line). (E) Same as D but for for the Cα–Cαinteraction; (F) same as D but for the Cβ–Cβ interaction.

Mentions: Some examples of the derived nonbonded potential functionsareshown in Figure 5A–C for the val–valsystem. For the most part, the potential functions have shapes thatare intuitively reasonable, with only a few small peaks and troughsat long distances that challenge easy interpretation. Most notably,however, the COFFDROP optimized potential functions (blue lines) aremuch less favorable and less long-ranged than the corresponding potentialfunctions that are obtained by performing a Boltzmann inversion ofthe MD g(r)s according to E = −RT ln g(r) (red lines). The need for the iterative adjustment ofthe potential functions so that they properly reproduce the g(r)s (shown in Figure 5D–F) is therefore clear (see Discussion).


COFFDROP: A Coarse-Grained Nonbonded Force Field for Proteins Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of Amino Acids.

Andrews CT, Elcock AH - J Chem Theory Comput (2014)

Example nonbonded potential functions. (A) Plot comparing the Ace–Acenonbonded potential function of the val–val system obtainedfrom IBI (blue) with that obtained from noniterative Boltzmann inversion(red) of the MD g(r) function. (B)Same as A but for the Cα–Cα interaction; (C) sameas A but for the Cβ–Cβ interaction. (D) Plot comparingthe Ace–Ace g(r) of the val-valsystem obtained from MD (black circles) with that obtained from BDusing COFFDROP (blue line). (E) Same as D but for for the Cα–Cαinteraction; (F) same as D but for the Cβ–Cβ interaction.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230375&req=5

fig5: Example nonbonded potential functions. (A) Plot comparing the Ace–Acenonbonded potential function of the val–val system obtainedfrom IBI (blue) with that obtained from noniterative Boltzmann inversion(red) of the MD g(r) function. (B)Same as A but for the Cα–Cα interaction; (C) sameas A but for the Cβ–Cβ interaction. (D) Plot comparingthe Ace–Ace g(r) of the val-valsystem obtained from MD (black circles) with that obtained from BDusing COFFDROP (blue line). (E) Same as D but for for the Cα–Cαinteraction; (F) same as D but for the Cβ–Cβ interaction.
Mentions: Some examples of the derived nonbonded potential functionsareshown in Figure 5A–C for the val–valsystem. For the most part, the potential functions have shapes thatare intuitively reasonable, with only a few small peaks and troughsat long distances that challenge easy interpretation. Most notably,however, the COFFDROP optimized potential functions (blue lines) aremuch less favorable and less long-ranged than the corresponding potentialfunctions that are obtained by performing a Boltzmann inversion ofthe MD g(r)s according to E = −RT ln g(r) (red lines). The need for the iterative adjustment ofthe potential functions so that they properly reproduce the g(r)s (shown in Figure 5D–F) is therefore clear (see Discussion).

Bottom Line: In a first test of the force field, it was used to predict the clustering behavior of concentrated amino acid solutions; the predictions were directly compared with the results of corresponding all-atom explicit-solvent MD simulations and found to be in excellent agreement.The anomalously strong intermolecular interactions seen in the MD study were reproduced in the COFFDROP simulations; a simple scaling of COFFDROP's nonbonded parameters, however, produced results in better accordance with experiment.Overall, our results suggest that potential functions derived from simulations of pairwise amino acid interactions might be of quite broad applicability, with COFFDROP likely to be especially useful for modeling unfolded or intrinsically disordered proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States.

ABSTRACT
We describe the derivation of a set of bonded and nonbonded coarse-grained (CG) potential functions for use in implicit-solvent Brownian dynamics (BD) simulations of proteins derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acids. Bonded potential functions were derived from 1 μs MD simulations of each of the 20 canonical amino acids, with histidine modeled in both its protonated and neutral forms; nonbonded potential functions were derived from 1 μs MD simulations of every possible pairing of the amino acids (231 different systems). The angle and dihedral probability distributions and radial distribution functions sampled during MD were used to optimize a set of CG potential functions through use of the iterative Boltzmann inversion (IBI) method. The optimized set of potential functions-which we term COFFDROP (COarse-grained Force Field for Dynamic Representation Of Proteins)-quantitatively reproduced all of the "target" MD distributions. In a first test of the force field, it was used to predict the clustering behavior of concentrated amino acid solutions; the predictions were directly compared with the results of corresponding all-atom explicit-solvent MD simulations and found to be in excellent agreement. In a second test, BD simulations of the small protein villin headpiece were carried out at concentrations that have recently been studied in all-atom explicit-solvent MD simulations by Petrov and Zagrovic (PLoS Comput. Biol. 2014, 5, e1003638). The anomalously strong intermolecular interactions seen in the MD study were reproduced in the COFFDROP simulations; a simple scaling of COFFDROP's nonbonded parameters, however, produced results in better accordance with experiment. Overall, our results suggest that potential functions derived from simulations of pairwise amino acid interactions might be of quite broad applicability, with COFFDROP likely to be especially useful for modeling unfolded or intrinsically disordered proteins.

No MeSH data available.


Related in: MedlinePlus