Evaluation of Reduced Point Charge Models of Proteins through Molecular Dynamics Simulations: Application to the Vps27 UIM-1 – Ubiquitin Complex

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Abstract

Reduced point charge models of amino acids are designed, (i) from local extrema positions in charge density distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential (MEP) functions, and (ii) from local maxima positions in promolecular electron density distribution functions. Corresponding charge values are fitted versus all-atom Amber99 MEPs. To easily generate reduced point charge models for protein structures, libraries of amino acid templates are built. The program GROMACS is used to generate stable molecular dynamics trajectories of an Ubiquitin-ligand complex (PDB: 1Q0W), under various implementation schemes, solvation, and temperature conditions. Point charges that are not located on atoms are considered as virtual sites with a nul mass and radius. The results illustrate how the intra- and inter-molecular H-bond interactions are affected by the degree of reduction of the point charge models and give directions for their implementation; a special attention to the atoms selected to locate the virtual sites and to the Coulomb-14 interactions is needed. Results obtained at various temperatures suggest that the use of reduced point charge models allows to probe local potential hyper-surface minima that are similar to the all-atom ones, but are characterized by lower energy barriers. It enables allows to generate various conformations of the protein complex more rapidly than the all-atom point charge representation.
Original languageEnglish
Pages (from-to)44-61
Number of pages17
JournalJournal of Molecular Graphics and Modelling
Volume47
Publication statusPublished - 2014

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Ubiquitin
Molecular dynamics
molecular dynamics
proteins
Proteins
Atoms
evaluation
Computer simulation
atoms
simulation
Probability density function
Distribution functions
amino acids
density distribution
Amino acids
distribution functions
Amino Acids
Electronic density of states
Energy barriers
Poisson equation

Keywords

  • Molecular electrostatic potential
  • Ubiquitin complex
  • protein
  • point charge model
  • critical points
  • smoothing of molecular fields
  • electron density

Cite this

@article{4707a0194a0c4ef0baba3aab04c25d7b,
title = "Evaluation of Reduced Point Charge Models of Proteins through Molecular Dynamics Simulations: Application to the Vps27 UIM-1 – Ubiquitin Complex",
abstract = "Reduced point charge models of amino acids are designed, (i) from local extrema positions in charge density distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential (MEP) functions, and (ii) from local maxima positions in promolecular electron density distribution functions. Corresponding charge values are fitted versus all-atom Amber99 MEPs. To easily generate reduced point charge models for protein structures, libraries of amino acid templates are built. The program GROMACS is used to generate stable molecular dynamics trajectories of an Ubiquitin-ligand complex (PDB: 1Q0W), under various implementation schemes, solvation, and temperature conditions. Point charges that are not located on atoms are considered as virtual sites with a nul mass and radius. The results illustrate how the intra- and inter-molecular H-bond interactions are affected by the degree of reduction of the point charge models and give directions for their implementation; a special attention to the atoms selected to locate the virtual sites and to the Coulomb-14 interactions is needed. Results obtained at various temperatures suggest that the use of reduced point charge models allows to probe local potential hyper-surface minima that are similar to the all-atom ones, but are characterized by lower energy barriers. It enables allows to generate various conformations of the protein complex more rapidly than the all-atom point charge representation.",
keywords = "Molecular electrostatic potential, Ubiquitin complex, protein, point charge model, critical points, smoothing of molecular fields, electron density",
author = "Laurence Leherte and Daniel Vercauteren",
year = "2014",
language = "English",
volume = "47",
pages = "44--61",
journal = "Journal of Molecular Graphics and Modelling",
issn = "1093-3263",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Evaluation of Reduced Point Charge Models of Proteins through Molecular Dynamics Simulations: Application to the Vps27 UIM-1 – Ubiquitin Complex

AU - Leherte, Laurence

AU - Vercauteren, Daniel

PY - 2014

Y1 - 2014

N2 - Reduced point charge models of amino acids are designed, (i) from local extrema positions in charge density distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential (MEP) functions, and (ii) from local maxima positions in promolecular electron density distribution functions. Corresponding charge values are fitted versus all-atom Amber99 MEPs. To easily generate reduced point charge models for protein structures, libraries of amino acid templates are built. The program GROMACS is used to generate stable molecular dynamics trajectories of an Ubiquitin-ligand complex (PDB: 1Q0W), under various implementation schemes, solvation, and temperature conditions. Point charges that are not located on atoms are considered as virtual sites with a nul mass and radius. The results illustrate how the intra- and inter-molecular H-bond interactions are affected by the degree of reduction of the point charge models and give directions for their implementation; a special attention to the atoms selected to locate the virtual sites and to the Coulomb-14 interactions is needed. Results obtained at various temperatures suggest that the use of reduced point charge models allows to probe local potential hyper-surface minima that are similar to the all-atom ones, but are characterized by lower energy barriers. It enables allows to generate various conformations of the protein complex more rapidly than the all-atom point charge representation.

AB - Reduced point charge models of amino acids are designed, (i) from local extrema positions in charge density distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential (MEP) functions, and (ii) from local maxima positions in promolecular electron density distribution functions. Corresponding charge values are fitted versus all-atom Amber99 MEPs. To easily generate reduced point charge models for protein structures, libraries of amino acid templates are built. The program GROMACS is used to generate stable molecular dynamics trajectories of an Ubiquitin-ligand complex (PDB: 1Q0W), under various implementation schemes, solvation, and temperature conditions. Point charges that are not located on atoms are considered as virtual sites with a nul mass and radius. The results illustrate how the intra- and inter-molecular H-bond interactions are affected by the degree of reduction of the point charge models and give directions for their implementation; a special attention to the atoms selected to locate the virtual sites and to the Coulomb-14 interactions is needed. Results obtained at various temperatures suggest that the use of reduced point charge models allows to probe local potential hyper-surface minima that are similar to the all-atom ones, but are characterized by lower energy barriers. It enables allows to generate various conformations of the protein complex more rapidly than the all-atom point charge representation.

KW - Molecular electrostatic potential

KW - Ubiquitin complex

KW - protein

KW - point charge model

KW - critical points

KW - smoothing of molecular fields

KW - electron density

M3 - Article

VL - 47

SP - 44

EP - 61

JO - Journal of Molecular Graphics and Modelling

JF - Journal of Molecular Graphics and Modelling

SN - 1093-3263

ER -