How accurately do force fields represent protein side chain ensembles?

2018 ◽  
Vol 86 (9) ◽  
pp. 935-944 ◽  
Author(s):  
Dušan Petrović ◽  
Xue Wang ◽  
Birgit Strodel
Keyword(s):  
Force Fields ◽  
Side Chain

Evaluating the London Dispersion Coefficients of Protein Force Fields Using the Exchange-Hole Dipole Moment Model

2018 ◽  
Author(s):  
Evan T. Walters ◽  
Mohamad Mohebifar ◽  
Erin R. Johnson ◽  
Christopher Rowley
Keyword(s):  
Dipole Moment ◽  
Force Fields ◽  
Higher Order ◽  
Side Chain ◽  
Dispersion Interactions ◽  
Dispersion Coefficients ◽  
Hydration Energies ◽  
London Dispersion ◽  
Higher Order Dispersion ◽  
Order Dispersion

<div>London dispersion is one of the fundamental intermolecular interactions involved in protein folding and dynamics. The popular CHARMM36, Amber ff14sb, and OPLS-</div><div>AA force fields represent these interactions through the C6 /r 6 term of the Lennard-Jones potential. The C6 parameters are assigned empirically, so these parameters are</div><div>not necessarily a realistic representation of the true dispersion interactions. In this work, dispersion coefficients of all three force fields were compared to corresponding</div><div>values from quantum-chemical calculations using the exchange-hole dipole moment (XDM) model. The force field values were found to be roughly 50% larger than the XDM values for protein backbone and side-chain models. The CHARMM36 and Amber OL15 force fields for nucleic acids were also found to exhibit this trend. To explore how these elevated dispersion coefficients affect predicted properties, the hydration energies of the side-chain models were calculated using the staged REMD-TI method of Deng and Roux for the CHARMM36, Amber ff14sb, and OPLS-AA force fields. Despite having large C 6 dispersion coefficients, these force fields predict side-chain hydration energies that are in generally good agreement with the experimental values, including for hydrocarbon residues where the dispersion component is the dominant attractive solute–solvent interaction. This suggests that these force fields predict the correct total strength of dispersion interactions, despite C6 coefficients that are considerably larger than XDM predicts. An analytical expression for the water–methane dispersion energy using XDM dispersion coefficients shows that that higher-order dispersion terms(i.e., C 8 and C 10 ) account for roughly 37.5% of the hydration energy of methane. This suggests that the C 6 dispersion coefficients used in contemporary force fields are</div><div>elevated to account for the neglected higher-order terms. Force fields that include higher-order dispersion interactions could resolve this issue.</div>

scholarly journals Protein side chain modeling with orientation‐dependent atomic force fields derived by series expansions

2011 ◽  
Vol 32 (8) ◽  
pp. 1680-1686 ◽  
Author(s):  
Shide Liang ◽  
Yaoqi Zhou ◽  
Nick Grishin ◽  
Daron M. Standley
Keyword(s):  
Force Fields ◽  
Side Chain ◽  
Series Expansions ◽  
Atomic Force

scholarly journals On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain order parameters

2016 ◽  
Vol 25 (6) ◽  
pp. 1156-1160 ◽  
Author(s):  
Evan S. O'Brien ◽  
A. Joshua Wand ◽  
Kim A. Sharp
Keyword(s):  
Molecular Dynamics ◽  
Force Fields ◽  
Order Parameters ◽  
Side Chain ◽  
Chain Order

Evaluating the London Dispersion Coefficients of Protein Force Fields Using the Exchange-Hole Dipole Moment Model

2018 ◽  
Author(s):  
Evan T. Walters ◽  
Mohamad Mohebifar ◽  
Erin R. Johnson ◽  
Christopher Rowley
Keyword(s):  
Dipole Moment ◽  
Force Fields ◽  
Higher Order ◽  
Side Chain ◽  
Dispersion Interactions ◽  
Dispersion Coefficients ◽  
Hydration Energies ◽  
London Dispersion ◽  
Higher Order Dispersion ◽  
Order Dispersion

<div>London dispersion is one of the fundamental intermolecular interactions involved in protein folding and dynamics. The popular CHARMM36, Amber ff14sb, and OPLS-</div><div>AA force fields represent these interactions through the C6 /r 6 term of the Lennard-Jones potential. The C6 parameters are assigned empirically, so these parameters are</div><div>not necessarily a realistic representation of the true dispersion interactions. In this work, dispersion coefficients of all three force fields were compared to corresponding</div><div>values from quantum-chemical calculations using the exchange-hole dipole moment (XDM) model. The force field values were found to be roughly 50% larger than the XDM values for protein backbone and side-chain models. The CHARMM36 and Amber OL15 force fields for nucleic acids were also found to exhibit this trend. To explore how these elevated dispersion coefficients affect predicted properties, the hydration energies of the side-chain models were calculated using the staged REMD-TI method of Deng and Roux for the CHARMM36, Amber ff14sb, and OPLS-AA force fields. Despite having large C 6 dispersion coefficients, these force fields predict side-chain hydration energies that are in generally good agreement with the experimental values, including for hydrocarbon residues where the dispersion component is the dominant attractive solute–solvent interaction. This suggests that these force fields predict the correct total strength of dispersion interactions, despite C6 coefficients that are considerably larger than XDM predicts. An analytical expression for the water–methane dispersion energy using XDM dispersion coefficients shows that that higher-order dispersion terms(i.e., C 8 and C 10 ) account for roughly 37.5% of the hydration energy of methane. This suggests that the C 6 dispersion coefficients used in contemporary force fields are</div><div>elevated to account for the neglected higher-order terms. Force fields that include higher-order dispersion interactions could resolve this issue.</div>

Evaluating the London Dispersion Coefficients of Protein Force Fields Using the Exchange-Hole Dipole Moment Model

2018 ◽  
Author(s):  
Evan T. Walters ◽  
Mohamad Mohebifar ◽  
Erin R. Johnson ◽  
Christopher Rowley
Keyword(s):  
Dipole Moment ◽  
Force Fields ◽  
Higher Order ◽  
Side Chain ◽  
Dispersion Interactions ◽  
Dispersion Coefficients ◽  
Hydration Energies ◽  
London Dispersion ◽  
Higher Order Dispersion ◽  
Order Dispersion

<div>London dispersion is one of the fundamental intermolecular interactions involved in protein folding and dynamics. The popular CHARMM36, Amber ff14sb, and OPLS-</div><div>AA force fields represent these interactions through the C6 /r 6 term of the Lennard-Jones potential. The C6 parameters are assigned empirically, so these parameters are</div><div>not necessarily a realistic representation of the true dispersion interactions. In this work, dispersion coefficients of all three force fields were compared to corresponding</div><div>values from quantum-chemical calculations using the exchange-hole dipole moment (XDM) model. The force field values were found to be roughly 50% larger than the XDM values for protein backbone and side-chain models. The CHARMM36 and Amber OL15 force fields for nucleic acids were also found to exhibit this trend. To explore how these elevated dispersion coefficients affect predicted properties, the hydration energies of the side-chain models were calculated using the staged REMD-TI method of Deng and Roux for the CHARMM36, Amber ff14sb, and OPLS-AA force fields. Despite having large C 6 dispersion coefficients, these force fields predict side-chain hydration energies that are in generally good agreement with the experimental values, including for hydrocarbon residues where the dispersion component is the dominant attractive solute–solvent interaction. This suggests that these force fields predict the correct total strength of dispersion interactions, despite C6 coefficients that are considerably larger than XDM predicts. An analytical expression for the water–methane dispersion energy using XDM dispersion coefficients shows that that higher-order dispersion terms(i.e., C 8 and C 10 ) account for roughly 37.5% of the hydration energy of methane. This suggests that the C 6 dispersion coefficients used in contemporary force fields are</div><div>elevated to account for the neglected higher-order terms. Force fields that include higher-order dispersion interactions could resolve this issue.</div>

scholarly journals Changes in the Local Conformational States Caused by Simple Na+ and K+ Ions in Polyelectrolyte Simulations: Comparison of Seven Force Fields with and without NBFIX and ECC Corrections

Polymers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 252
Author(s):  
Natalia Lukasheva ◽  
Dmitry Tolmachev ◽  
Hector Martinez-Seara ◽  
Mikko Karttunen
Keyword(s):  
Experimental Data ◽  
Electrostatic Interactions ◽  
Force Fields ◽  
Dynamic Properties ◽  
Water Solution ◽  
Md Simulations ◽  
Side Chain ◽  
Local Structures ◽  
Structure And Dynamics ◽  
Molecular Sizes

Electrostatic interactions have a determining role in the conformational and dynamic behavior of polyelectrolyte molecules. In this study, anionic polyelectrolyte molecules, poly(glutamic acid) (PGA) and poly(aspartic acid) (PASA), in a water solution with the most commonly used K+ or Na+ counterions, were investigated using atomistic molecular dynamics (MD) simulations. We performed a comparison of seven popular force fields, namely AMBER99SB-ILDN, AMBER14SB, AMBER-FB15, CHARMM22*, CHARMM27, CHARMM36m and OPLS-AA/L, both with their native parameters and using two common corrections for overbinding of ions, the non-bonded fix (NBFIX), and electronic continuum corrections (ECC). These corrections were originally introduced to correct for the often-reported problem concerning the overbinding of ions to the charged groups of polyelectrolytes. In this work, a comparison of the simulation results with existing experimental data revealed several differences between the investigated force fields. The data from these simulations and comparisons with previous experimental data were then used to determine the limitations and strengths of these force fields in the context of the structural and dynamic properties of anionic polyamino acids. Physical properties, such as molecular sizes, local structure, and dynamics, were studied using two types of common counterions, namely potassium and sodium. The results show that, in some cases, both the macroion size and dynamics depend strongly on the models (parameters) for the counterions due to strong overbinding of the ions and charged side chain groups. The local structures and dynamics are more sensitive to dihedral angle parameterization, resulting in a preference for defined monomer conformations and the type of correction used. We also provide recommendations based on the results.

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