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Improved Peptide and Protein Torsional Energetics with the OPLS-AA Force Field.

Robertson MJ, Tirado-Rives J, Jorgensen WL - J Chem Theory Comput (2015)

Bottom Line: New Fourier coefficients for the dihedral angle terms of the OPLS-AA force field were fit to these surfaces, utilizing a Boltzmann-weighted error function and systematically examining the effects of weighting temperature.Extensive experimental solution-phase and quantum chemical gas-phase benchmarks were used to assess the quality of the new parameters, named OPLS-AA/M, demonstrating significant improvement over previous OPLS-AA force fields.Conclusions are drawn from the results for best practices for developing new torsion parameters for protein force fields.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.

ABSTRACT

The development and validation of new peptide dihedral parameters are reported for the OPLS-AA force field. High accuracy quantum chemical methods were used to scan φ, ψ, χ1, and χ2 potential energy surfaces for blocked dipeptides. New Fourier coefficients for the dihedral angle terms of the OPLS-AA force field were fit to these surfaces, utilizing a Boltzmann-weighted error function and systematically examining the effects of weighting temperature. To prevent overfitting to the available data, a minimal number of new residue-specific and peptide-specific torsion terms were developed. Extensive experimental solution-phase and quantum chemical gas-phase benchmarks were used to assess the quality of the new parameters, named OPLS-AA/M, demonstrating significant improvement over previous OPLS-AA force fields. A Boltzmann weighting temperature of 2000 K was determined to be optimal for fitting the new Fourier coefficients for dihedral angle parameters. Conclusions are drawn from the results for best practices for developing new torsion parameters for protein force fields.

No MeSH data available.


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Diagram of the definitionof rotamers m/t/p employed in this work.
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fig1: Diagram of the definitionof rotamers m/t/p employed in this work.

Mentions: Triplicate 205 ns simulations were run for an unblocked alanine pentapeptide(Ala5) with and glycine tripeptide (Gly3) withprotonated C-termini with the first 5 ns discarded as equilibration.The remaining amino acids, with the exception of proline, were simulatedfor 205 ns as blocked dipeptides, again in triplicate with the first5 ns discarded as equilibration. Values and error bars throughoutthe paper represent the mean and standard deviation of the calculatedquantities from the triplicate runs. Ala5 and Gly3 simulations were run with each of the four weighting temperaturesexamined in this work, as well as the previous OPLS-AA and OPLS-AA/Lforce field. Dipeptide simulations were performed with OPLS-AA, OPLS-AA/L,and the new parameters optimized at 2000 K. As each system was studiedfor 600 ns with at least three different force fields, over 50 μsof validating simulations have been executed. In analyzing the moleculardynamics simulations for the short alanine and glycine peptides, thedefinitions of secondary structure, the three sets of Karplus parametersfor calculating J couplings, and the experimentalerror values used to calculate χ2 from Best et al.42 were employed. For the dipeptide simulations,only the first set of Karplus parameters, that of Hu and Bax,43 was employed. χ1 rotamer populationswere determined by dividing the range of χ1 valuesinto three equal sized bins, corresponding to the p (+60°), t(180°) and m (−60°) conformers. Definitions of p,t, and m for valine, isoleucine, and threonine were adopted from thework of Dunbrak and co-workers27 and aredepicted in Figure 1.


Improved Peptide and Protein Torsional Energetics with the OPLS-AA Force Field.

Robertson MJ, Tirado-Rives J, Jorgensen WL - J Chem Theory Comput (2015)

Diagram of the definitionof rotamers m/t/p employed in this work.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4504185&req=5

fig1: Diagram of the definitionof rotamers m/t/p employed in this work.
Mentions: Triplicate 205 ns simulations were run for an unblocked alanine pentapeptide(Ala5) with and glycine tripeptide (Gly3) withprotonated C-termini with the first 5 ns discarded as equilibration.The remaining amino acids, with the exception of proline, were simulatedfor 205 ns as blocked dipeptides, again in triplicate with the first5 ns discarded as equilibration. Values and error bars throughoutthe paper represent the mean and standard deviation of the calculatedquantities from the triplicate runs. Ala5 and Gly3 simulations were run with each of the four weighting temperaturesexamined in this work, as well as the previous OPLS-AA and OPLS-AA/Lforce field. Dipeptide simulations were performed with OPLS-AA, OPLS-AA/L,and the new parameters optimized at 2000 K. As each system was studiedfor 600 ns with at least three different force fields, over 50 μsof validating simulations have been executed. In analyzing the moleculardynamics simulations for the short alanine and glycine peptides, thedefinitions of secondary structure, the three sets of Karplus parametersfor calculating J couplings, and the experimentalerror values used to calculate χ2 from Best et al.42 were employed. For the dipeptide simulations,only the first set of Karplus parameters, that of Hu and Bax,43 was employed. χ1 rotamer populationswere determined by dividing the range of χ1 valuesinto three equal sized bins, corresponding to the p (+60°), t(180°) and m (−60°) conformers. Definitions of p,t, and m for valine, isoleucine, and threonine were adopted from thework of Dunbrak and co-workers27 and aredepicted in Figure 1.

Bottom Line: New Fourier coefficients for the dihedral angle terms of the OPLS-AA force field were fit to these surfaces, utilizing a Boltzmann-weighted error function and systematically examining the effects of weighting temperature.Extensive experimental solution-phase and quantum chemical gas-phase benchmarks were used to assess the quality of the new parameters, named OPLS-AA/M, demonstrating significant improvement over previous OPLS-AA force fields.Conclusions are drawn from the results for best practices for developing new torsion parameters for protein force fields.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.

ABSTRACT

The development and validation of new peptide dihedral parameters are reported for the OPLS-AA force field. High accuracy quantum chemical methods were used to scan φ, ψ, χ1, and χ2 potential energy surfaces for blocked dipeptides. New Fourier coefficients for the dihedral angle terms of the OPLS-AA force field were fit to these surfaces, utilizing a Boltzmann-weighted error function and systematically examining the effects of weighting temperature. To prevent overfitting to the available data, a minimal number of new residue-specific and peptide-specific torsion terms were developed. Extensive experimental solution-phase and quantum chemical gas-phase benchmarks were used to assess the quality of the new parameters, named OPLS-AA/M, demonstrating significant improvement over previous OPLS-AA force fields. A Boltzmann weighting temperature of 2000 K was determined to be optimal for fitting the new Fourier coefficients for dihedral angle parameters. Conclusions are drawn from the results for best practices for developing new torsion parameters for protein force fields.

No MeSH data available.


Related in: MedlinePlus