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ff14ipq: A Self-Consistent Force Field for Condensed-Phase Simulations of Proteins.

Cerutti DS, Swope WC, Rice JE, Case DA - J Chem Theory Comput (2014)

Bottom Line: The force field gives strong performance on α-helical and β-sheet oligopeptides as well as globular proteins over microsecond time scale simulations, although it has not yet been tested in conjunction with lipid and nucleic acid models.We show how our choices in parameter development influence the resulting force field and how other choices that may have appeared reasonable would actually have led to poorer results.The tools we developed may also aid in the development of future fixed-charge and even polarizable biomolecular force fields.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Biology and BioMaPS Institute, Rutgers University , 610 Taylor Road, Piscataway, New Jersey 08854-8066, United States.

ABSTRACT
We present the ff14ipq force field, implementing the previously published IPolQ charge set for simulations of complete proteins. Minor modifications to the charge derivation scheme and van der Waals interactions between polar atoms are introduced. Torsion parameters are developed through a generational learning approach, based on gas-phase MP2/cc-pVTZ single-point energies computed of structures optimized by the force field itself rather than the quantum benchmark. In this manner, we sacrifice information about the true quantum minima in order to ensure that the force field maintains optimal agreement with the MP2/cc-pVTZ benchmark for the ensembles it will actually produce in simulations. A means of making the gas-phase torsion parameters compatible with solution-phase IPolQ charges is presented. The ff14ipq model is an alternative to ff99SB and other Amber force fields for protein simulations in programs that accommodate pair-specific Lennard-Jones combining rules. The force field gives strong performance on α-helical and β-sheet oligopeptides as well as globular proteins over microsecond time scale simulations, although it has not yet been tested in conjunction with lipid and nucleic acid models. We show how our choices in parameter development influence the resulting force field and how other choices that may have appeared reasonable would actually have led to poorer results. The tools we developed may also aid in the development of future fixed-charge and even polarizable biomolecular force fields.

No MeSH data available.


Related in: MedlinePlus

Backbone positionalroot-mean-squared deviations (rmsds) for TrpCage miniprotein simulations. Simulations of each of two Trp Cageproteins are indicated by their respective PDB codes. The top panelshows overall backbone rmsd to the first published NMR model for eachsystem. Lower panels show histograms of per-residue backbone rmsdto the closest possible match out of all published NMR models, darkenedto indicate increasing occupancy at a particular deviation.
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fig12: Backbone positionalroot-mean-squared deviations (rmsds) for TrpCage miniprotein simulations. Simulations of each of two Trp Cageproteins are indicated by their respective PDB codes. The top panelshows overall backbone rmsd to the first published NMR model for eachsystem. Lower panels show histograms of per-residue backbone rmsdto the closest possible match out of all published NMR models, darkenedto indicate increasing occupancy at a particular deviation.

Mentions: As shown in Figure 12, both Trp Cagesimulationsshowed very stable backbone configurations over the 500 ns simulations.The baseline rmsd of approximately 1.2 Å may indicate differentpreferences of the IPolQ charge set compared to the parameters usedin NMR refinement, but larger departures from the backbone configurationdepicted in the NMR models were merely transient. Figure 12 shows histograms of per-residue backbone positionrmsds as were calculated for chignolin. Most residues display lowrmsds under this test, and most importantly the Pro-Pro-Pro sequencenear the C-terminus remains stable. Some residues, in particular theAsp-Gly-Gly-Pro sequence in simulations of Neidigh’s Trp Cage(PDB code 1L2Y(45)), show a weakly bimodal distribution,suggesting that the simulations explore an alternate conformationnot seen in the NMR ensemble. When simulating a hyperstable Trp Cagemutant (PDB code 1RIJ(46)), the Asp-Gly-Gly-Pro sequence againdeparts from the NMR ensemble more significantly than other regionsof the protein. The conformations of these residues are good candidatesfor future analysis and refinement of ff14ipq.


ff14ipq: A Self-Consistent Force Field for Condensed-Phase Simulations of Proteins.

Cerutti DS, Swope WC, Rice JE, Case DA - J Chem Theory Comput (2014)

Backbone positionalroot-mean-squared deviations (rmsds) for TrpCage miniprotein simulations. Simulations of each of two Trp Cageproteins are indicated by their respective PDB codes. The top panelshows overall backbone rmsd to the first published NMR model for eachsystem. Lower panels show histograms of per-residue backbone rmsdto the closest possible match out of all published NMR models, darkenedto indicate increasing occupancy at a particular deviation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196740&req=5

fig12: Backbone positionalroot-mean-squared deviations (rmsds) for TrpCage miniprotein simulations. Simulations of each of two Trp Cageproteins are indicated by their respective PDB codes. The top panelshows overall backbone rmsd to the first published NMR model for eachsystem. Lower panels show histograms of per-residue backbone rmsdto the closest possible match out of all published NMR models, darkenedto indicate increasing occupancy at a particular deviation.
Mentions: As shown in Figure 12, both Trp Cagesimulationsshowed very stable backbone configurations over the 500 ns simulations.The baseline rmsd of approximately 1.2 Å may indicate differentpreferences of the IPolQ charge set compared to the parameters usedin NMR refinement, but larger departures from the backbone configurationdepicted in the NMR models were merely transient. Figure 12 shows histograms of per-residue backbone positionrmsds as were calculated for chignolin. Most residues display lowrmsds under this test, and most importantly the Pro-Pro-Pro sequencenear the C-terminus remains stable. Some residues, in particular theAsp-Gly-Gly-Pro sequence in simulations of Neidigh’s Trp Cage(PDB code 1L2Y(45)), show a weakly bimodal distribution,suggesting that the simulations explore an alternate conformationnot seen in the NMR ensemble. When simulating a hyperstable Trp Cagemutant (PDB code 1RIJ(46)), the Asp-Gly-Gly-Pro sequence againdeparts from the NMR ensemble more significantly than other regionsof the protein. The conformations of these residues are good candidatesfor future analysis and refinement of ff14ipq.

Bottom Line: The force field gives strong performance on α-helical and β-sheet oligopeptides as well as globular proteins over microsecond time scale simulations, although it has not yet been tested in conjunction with lipid and nucleic acid models.We show how our choices in parameter development influence the resulting force field and how other choices that may have appeared reasonable would actually have led to poorer results.The tools we developed may also aid in the development of future fixed-charge and even polarizable biomolecular force fields.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Biology and BioMaPS Institute, Rutgers University , 610 Taylor Road, Piscataway, New Jersey 08854-8066, United States.

ABSTRACT
We present the ff14ipq force field, implementing the previously published IPolQ charge set for simulations of complete proteins. Minor modifications to the charge derivation scheme and van der Waals interactions between polar atoms are introduced. Torsion parameters are developed through a generational learning approach, based on gas-phase MP2/cc-pVTZ single-point energies computed of structures optimized by the force field itself rather than the quantum benchmark. In this manner, we sacrifice information about the true quantum minima in order to ensure that the force field maintains optimal agreement with the MP2/cc-pVTZ benchmark for the ensembles it will actually produce in simulations. A means of making the gas-phase torsion parameters compatible with solution-phase IPolQ charges is presented. The ff14ipq model is an alternative to ff99SB and other Amber force fields for protein simulations in programs that accommodate pair-specific Lennard-Jones combining rules. The force field gives strong performance on α-helical and β-sheet oligopeptides as well as globular proteins over microsecond time scale simulations, although it has not yet been tested in conjunction with lipid and nucleic acid models. We show how our choices in parameter development influence the resulting force field and how other choices that may have appeared reasonable would actually have led to poorer results. The tools we developed may also aid in the development of future fixed-charge and even polarizable biomolecular force fields.

No MeSH data available.


Related in: MedlinePlus