Validation of the GROMOS 54A7 Force Field Regarding Mixed <i>α</i>/<i>β</i>‐Peptide Molecules

Wang, Dongqi; Freitag, Fabian; Gattin, Zrinka; Haberkern, Hannah; Jaun, Bernhard; Siwko, Magdalena E.; Vyas, Rounak; Gunsteren, Wilfred F. van; Dolenc, Jožica

doi:10.1002/hlca.201200534

Cited by 11 publications

(12 citation statements)

References 47 publications

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“…Unlike ab initio quantum mechanical (QM) methods, the classical MM models treat atoms as rigid particles with electronic degrees of freedom averaged out, thereby lowering the computational cost and allowing simulation of biological events for larger systems and longer time scales. On the other hand, high level ab initio theory is becoming more affordable and is now heavily utilized during the development of classic potentials for proteins such as Amber, 1 CFF, 2 CHARMM, 3 GROMOS, 4 MM3 5 and OPLS-AA. 6 This class of force field typically utilizes fixed atomic charges, point dispersion-repulsion, and simple empirical functions for valence interactions.…”

Section: Introductionmentioning

confidence: 99%

Polarizable Atomic Multipole-Based AMOEBA Force Field for Proteins

Shi

Xia

Zhang

et al. 2013

J. Chem. Theory Comput.

621

800

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Development of the AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Simulation) force field for proteins is presented. The current version (AMOEBA-2013) utilizes permanent electrostatic multipole moments through the quadrupole at each atom, and explicitly treats polarization effects in various chemical and physical environments. The atomic multipole electrostatic parameters for each amino acid residue type are derived from high-level gas phase quantum mechanical calculations via a consistent and extensible protocol. Molecular polarizability is modeled via a Thole-style damped interactive induction model based upon distributed atomic polarizabilities. Inter- and intramolecular polarization is treated in a consistent fashion via the Thole model. The intramolecular polarization model ensures transferability of electrostatic parameters among different conformations, as demonstrated by the agreement between QM and AMOEBA electrostatic potentials, and dipole moments of dipeptides. The backbone and side chain torsional parameters were determined by comparing to gas-phase QM (RI-TRIM MP2/CBS) conformational energies of dipeptides and to statistical distributions from the Protein Data Bank. Molecular dynamics simulations are reported for short peptides in explicit water to examine their conformational properties in solution. Overall the calculated conformational free energies and J-coupling constants are consistent with PDB statistics and experimental NMR results, respectively. In addition, the experimental crystal structures of a number of proteins are well maintained during molecular dynamics (MD) simulation. While further calculations are necessary to fully validate the force field, initial results suggest the AMOEBA polarizable multipole force field is able to describe the structure and energetics of peptides and proteins, in both gas-phase and solution environments.

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Section: Introductionmentioning

confidence: 99%

Polarizable Atomic Multipole-Based AMOEBA Force Field for Proteins

Shi

Xia

Zhang

et al. 2013

J. Chem. Theory Comput.

621

800

View full text Add to dashboard Cite

show abstract

“…To assess the performance and compare the reliability of the chosen three sets of parameters, the “VALXVAL” heptapeptide (Figure ), which has been used extensively in experimental and also in MD studies, was investigated. The dominant fold of this molecule in methanol was found by NMR experiments to be a 14‐helix (abbreviated H14, corresponding to an

i \to i + 2

intrachain hydrogen bond pattern, illustrated in the figure with dashed lines) …”

Section: Resultsmentioning

confidence: 99%

“…combined MD with NMR results on various β‐peptide secondary structures . They extended the GROMOS 54A7 united atom force field for β‐peptides by adding chemically analogous atom types and adjusting the non‐bonded FF parameters responsible for intrachain hydrogen bonding …”

Section: Introductionmentioning

confidence: 99%

“…[18,22,24,27,28] They extended the GROMOS 54A7 united atom force field for β-peptides by adding chemically analogous atom types and adjusting the non-bonded FF parameters responsible for intrachain hydrogen bonding. [29,30] For CHARMM22, Cui and coworkers optimized the barrier height parameters of the backbone torsion terms of β 3 -amino acids using a multiobjective optimization method. [31][32][33] Martinek et al compared the behavior of mainly cyclic βpeptides under the AMBER ff03 and the GAFF force fields using an explicit TIP3P water model.…”

Section: Introductionmentioning

confidence: 99%

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Improved Modeling of Peptidic Foldamers Using a Quantum Chemical Parametrization Based on Torsional Minimum Energy Path Matching

2019

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The increasing interest in novel foldamer constructs demands an accurate computational treatment on an extensive timescale. However, it is still a challenge to derive a force field (FF) that can reproduce the experimentally known fold while also allowing the spontaneous exploration of other structures. Here, aiming at a realistic reproduction of backbone torsional barriers, the relevant proper dihedrals of acyclic β 2 ‐, β 3 ‐ and β 2,3 ‐amino acids were added to the CHARMM FF and optimized using a novel, self‐consistent iterative procedure based on quantum chemical relaxed scans. The new FF was validated by molecular dynamics simulations on three acyclic peptides. While they resided most of the time in their preferred fold (>80 % in helices and >50 % in hairpin), they also visited other conformations. Owing to the CHARMM36m‐consistent parametrization, the proposed extension is suitable for exploring new foldamer structures and assemblies, and their interactions with diverse biomolecules.

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“…Compared with previous versions of the GROMOS force field, the 54A7 force field stabilizes the folds of both β‐peptides and the agreement of the simulated NOE atom‐atom distances with the experimental NMR data was slightly improved . Two other β‐peptides and two mixed α/β‐peptides were also simulated using the 54A7 force field and their dominant helical or hairpin folds and experimental data were reproduced …”

Section: Introductionmentioning

confidence: 99%

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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Validation of the GROMOS 54A7 Force Field Regarding Mixed α/β‐Peptide Molecules

Cited by 11 publications

References 47 publications

Polarizable Atomic Multipole-Based AMOEBA Force Field for Proteins

Polarizable Atomic Multipole-Based AMOEBA Force Field for Proteins

Improved Modeling of Peptidic Foldamers Using a Quantum Chemical Parametrization Based on Torsional Minimum Energy Path Matching

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

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