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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.


Clustering of alanine, leucine, asparagine,and tryptophan solutionsat concentrations of 200 and 300 mg/mL in MD and BD. Same as Figure 6 but showing results for much higher concentrations.
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fig7: Clustering of alanine, leucine, asparagine,and tryptophan solutionsat concentrations of 200 and 300 mg/mL in MD and BD. Same as Figure 6 but showing results for much higher concentrations.

Mentions: To further test the transferability of our nonbonded potentialfunctions to conditions that are even more different from those inwhich they were derived, additional 1 μs MD and BD simulationsof systems containing 50, 100, 200, or 300 mg/mL of capped amino acidswere also performed. To provide a range of interaction types and strengthsfor testing, these simulations were performed on ala, asn, leu andtrp systems. Shown in Figure 7 are the resultsof cluster analyses for each of these systems at 200 and 300 mg/mL;the results for 50 and 100 mg/mL can be found in Supporting Information Figure S12. Again, the correspondencebetween the results obtained from the all-atom MD and the coarse-grainedBD simulations is surprisingly good. For tryptophan at 200 and 300mg/mL, the BD simulations successfully reproduce the prediction fromMD that a single large cluster should form that traverses the widthof the simulation box (for a visual comparison of the MD and BD snapshotsof the 300 mg/mL trp system see Supporting InformationFigure S13). At lower concentrations, the BD simulations predicta degree of clustering that is somewhat too high relative to MD (Supporting Information Figure S12); this suggeststhat the solubility predicted by the pairwise CG potential functionsis somewhat lower than that predicted by the all-atom MD potentialfunctions. For the other three amino acids studied, agreement withMD is again good, but, interestingly, the BD simulations in thesecases predict a degree of clustering that is somewhat lower than thatpredicted by the MD simulations.


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)

Clustering of alanine, leucine, asparagine,and tryptophan solutionsat concentrations of 200 and 300 mg/mL in MD and BD. Same as Figure 6 but showing results for much higher concentrations.
© Copyright Policy
Related In: Results  -  Collection

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

fig7: Clustering of alanine, leucine, asparagine,and tryptophan solutionsat concentrations of 200 and 300 mg/mL in MD and BD. Same as Figure 6 but showing results for much higher concentrations.
Mentions: To further test the transferability of our nonbonded potentialfunctions to conditions that are even more different from those inwhich they were derived, additional 1 μs MD and BD simulationsof systems containing 50, 100, 200, or 300 mg/mL of capped amino acidswere also performed. To provide a range of interaction types and strengthsfor testing, these simulations were performed on ala, asn, leu andtrp systems. Shown in Figure 7 are the resultsof cluster analyses for each of these systems at 200 and 300 mg/mL;the results for 50 and 100 mg/mL can be found in Supporting Information Figure S12. Again, the correspondencebetween the results obtained from the all-atom MD and the coarse-grainedBD simulations is surprisingly good. For tryptophan at 200 and 300mg/mL, the BD simulations successfully reproduce the prediction fromMD that a single large cluster should form that traverses the widthof the simulation box (for a visual comparison of the MD and BD snapshotsof the 300 mg/mL trp system see Supporting InformationFigure S13). At lower concentrations, the BD simulations predicta degree of clustering that is somewhat too high relative to MD (Supporting Information Figure S12); this suggeststhat the solubility predicted by the pairwise CG potential functionsis somewhat lower than that predicted by the all-atom MD potentialfunctions. For the other three amino acids studied, agreement withMD is again good, but, interestingly, the BD simulations in thesecases predict a degree of clustering that is somewhat lower than thatpredicted by the MD simulations.

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.