Reoptimized interaction parameters for the peptide‐backbone model compound <i>N</i>‐methylacetamide in the GROMOS force field: Influence on the folding properties of two beta‐peptides in methanol

Horta, Bruno A. C.; Lin, Zhihua; Huang, Wei; Riniker, Sereina; Gunsteren, Wilfred F. van; Hünenberger, Philippe H.

doi:10.1002/jcc.23021

Cited by 14 publications

(35 citation statements)

References 53 publications

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“…a and e). This is in line with a slower folding‐unfolding kinetics observed in the simulation of another β‐peptide using 53A6 compared with the one using 45A3, whereas for the 54A7 force field (Figs. i and j), the picture is completely different.…”

Section: Resultssupporting

confidence: 84%

Refinement of the application of the GROMOS 54A7 force field to β-peptides

Lin

Gunsteren

2013

J. Comput. Chem.

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In this study, a hexa-β-peptide whose conformational equilibrium encompasses two different helical folds, a right-handed 2.7(10/12)-helix and a left-handed 3(14)-helix, is simulated using different GROMOS force-field parameter sets. When applying the recently developed GROMOS 54A7 force field, a significant destabilization effect on the 2.7(10/12)-helix of the peptide is observed, and the agreement with the experimental NOE distance bounds is much worse compared with the ones using previous versions of the GROMOS force field. This led us to investigate the free enthalpy difference between the two helices as a function of a variation of different subsets of force-field parameters. Both long time molecular dynamics simulations and one-step perturbation predictions suggest that the disagreement with the experimental NMR data when using the 54A7 force field is caused by the use for β-peptides of the new backbone φ-/ψ-torsional-angle energy terms introduced in this force field which were based on conformational fitting of backbone φ/ψ angles for a large set of proteins. This means that these parameters of backbone φ- and ψ-torsional-angle terms should not be applied to non-α-peptides such as β-peptides. This modified assignment of torsional-angle energy terms and parameters is denoted as 54A7_β. It corrects the wrong description of the conformational ensemble of the hexa-β-peptide obtained using the previous assignment and yields as good agreement with NMR data for other β-peptides that adopt a single helical or a hairpin fold.

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Section: Resultssupporting

confidence: 84%

Refinement of the application of the GROMOS 54A7 force field to β-peptides

Lin

Gunsteren

2013

J. Comput. Chem.

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“…Article developed GROMOS 53A6 OXY , 24 53A6 OXY+D , 25 and 53A6 OXY+A 80 force fields tackled this problem by using both liquid and solvation properties in the calibration.…”

Section: Journal Of Chemical Information and Modelingmentioning

confidence: 99%

Force Field Benchmark of Organic Liquids. 2. Gibbs Energy of Solvation

Jin

Tuguldur

Spoel

2015

J. Chem. Inf. Model.

146

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Quantitative prediction of physical properties of liquids is a longstanding goal of molecular simulation. Here, we evaluate the predictive power of the Generalized Amber Force Field (Wang et al. J. Comput. Chem. 2004, 25, 1157-1174) for the Gibbs energy of solvation of organic molecules in organic solvents using the thermodynamics integration (TI) method. The results are compared to experimental data, to a model based on quantitative structure property relations (QSPR), and to the conductor-like screening models for realistic solvation (COSMO-RS) model. Although the TI calculations yield slightly better correlation to experimental results than the other models, in all fairness we should conclude that the difference between the models is minor since both QSPR and COSMO-RS yield a slightly lower RMSD from that of the experiment (<3.5 kJ/mol). By analyzing which molecules (either as solvents or solutes) are outliers in the TI calculations, we can pinpoint where additional parametrization efforts are needed. For the force field based TI calculations, deviations from the experiment occur in particular when compounds containing nitro or ester groups are solvated into other liquids, suggesting that the interaction between these groups and solvents may be too strong. In the COSMO-RS calculations, outliers mainly occur when compounds containing (in particular aromatic) rings are solvated despite using a ring correction term in the calculations.

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“…The calculated values for the alcohols, the ketones, the carboxylic acids, the other amines, the amides and the disulfide are systematically underestimated compared to the experimental ones.The deviation is particularly large for the amides AMD, LNMA and DAMD, characterized by anomalously high experimental permittivities of 128 65.0, 139.5 and 37.8, respectively, reason for which their representative points are not displayed inFigure 3.The corresponding values calculated using 2016H66 are significantly lower, namely 30.3, 49.0 and 20.2, respectively. Note that the representation of amides and in particular of their dielectric properties within classical force fields is a challenging problem that has attracted considerable attention over the years 95,[208][209][210][211][212]. .…”

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confidence: 99%

A GROMOS-Compatible Force Field for Small Organic Molecules in the Condensed Phase: The 2016H66 Parameter Set

Horta

Merz

Fuchs

et al. 2016

J. Chem. Theory Comput.

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146

287

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This article reports on the calibration and validation of a new GROMOS-compatible parameter set 2016H66 for small organic molecules in the condensed phase. The calibration is based on 62 organic molecules spanning the chemical functions alcohol, ether, aldehyde, ketone, carboxylic acid, ester, amine, amide, thiol, sulfide, and disulfide, as well as aromatic compounds and nucleic-acid bases. For 57 organic compounds, the calibration targets are the experimental pure-liquid density ρliq and the vaporization enthalpy ΔHvap, as well as the hydration free energy ΔGwat and the solvation free energy ΔGche in cyclohexane, at atmospheric pressure and at (or close to) room temperature. The final root-mean-square deviations (RMSD) for these four quantities over the set of compounds are 32.4 kg m(-3), 3.5 kJ mol(-1), 4.1 kJ mol(-1), and 2.1 kJ mol(-1), respectively, and the corresponding average deviations (AVED) are 1.0 kg m(-3), 0.2 kJ mol(-1), 2.6 kJ mol(-1), and 1.0 kJ mol(-1), respectively. For the five nucleic-acid bases, the parametrization is performed by transferring the final 2016H66 parameters from analogous organic compounds followed by a slight readjustment of the charges to reproduce the experimental water-to-chloroform transfer free energies ΔGtrn. The final RMSD for this quantity over the five bases is 1.7 kJ mol(-1), and the corresponding AVED is 0.8 kJ mol(-1). As an initial validation of the 2016H66 set, seven additional thermodynamic, transport, and dielectric properties are calculated for the 57 organic compounds in the liquid phase. The agreement with experiment in terms of these additional properties is found to be reasonable, with significant deviations typically affecting either a specific chemical function or a specific molecule. This suggests that in most cases, a classical force-field description along with a careful parametrization against ρliq, ΔHvap, ΔGwat, and ΔGche results in a model that appropriately describes the liquid in terms of a wide spectrum of its physical properties.

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Reoptimized interaction parameters for the peptide‐backbone model compound N‐methylacetamide in the GROMOS force field: Influence on the folding properties of two beta‐peptides in methanol

Cited by 14 publications

References 53 publications

Refinement of the application of the GROMOS 54A7 force field to β-peptides

Refinement of the application of the GROMOS 54A7 force field to β-peptides

Force Field Benchmark of Organic Liquids. 2. Gibbs Energy of Solvation

A GROMOS-Compatible Force Field for Small Organic Molecules in the Condensed Phase: The 2016H66 Parameter Set

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