Reduced point charge models of proteins: Assessment based on molecular dynamics simulations

Research output: Contribution to journalArticle

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Abstract

A reduced point charge distribution is used to model Ubiquitin and two complexes, Vps27 UIM-1-Ubiquitin and Barnase-Barstar. It is designed from local extrema in charge density distributions obtained from the Poisson equation applied to smoothed molecular electrostatic potentials. A variant distribution is built by locating point charges on atoms. Various charge fitting conditions are selected, i.e. from either electrostatic Amber99 (Assisted Model Building with Energy Refinement) Coulomb potential or forces, considering reference grid points located within various distances from the protein atoms, with or without separate treatment of main and side chain charges. The program GROMACS (Groningen Machine for Chemical Simulations) is used to generate Amber99SB molecular dynamics (MD) trajectories of the solvated proteins modelled using the various reduced point charge models (RPCMs) so obtained. Point charges that are not located on atoms are considered as virtual sites. Some RPCMs lead to stable MD trajectories. They, however, involve a partial loss in the protein secondary structure and lead to a less-structured solute solvation shell. The model built by fitting charges on Coulomb forces calculated at grid points ranging between 1.4 and 2.0 times the van der Waals radius of the atoms, with a separate treatment of main chain and side chain charges, appears to best approximate all-atom MD trajectories.

Original languageEnglish
Pages (from-to)289-304
Number of pages16
JournalMolecular Simulation
Volume42
Issue number4
DOIs
Publication statusPublished - 2016

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Molecular Dynamics Simulation
Molecular dynamics
Charge
molecular dynamics
proteins
Proteins
Protein
Atoms
Computer simulation
Trajectories
atoms
trajectories
Ubiquitin
simulation
Electrostatics
grids
Molecular Dynamics
electrostatics
Model
Charge distribution

Keywords

  • Barnase-Barstar
  • molecular electrostatic potential
  • reduced point charge model
  • smoothing of molecular fields
  • Ubiquitin

Cite this

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Reduced point charge models of proteins: Assessment based on molecular dynamics simulations. / Leherte, Laurence.

In: Molecular Simulation, Vol. 42, No. 4, 2016, p. 289-304.

Research output: Contribution to journalArticle

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