Inter-ring rotation of apolipoprotein A-I protein monomers for the double-belt model using biased molecular dynamics

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23 Citations (Scopus)

Abstract

The double belt model for lipid-bound discoidal apolipoprotein A-I consists of two alpha-helical monomers bound about an unilamellar bilayer of lipids. Previous work, based on salt bridge calculations, has demonstrated that the L5/5 registration, Milano mutant, and Paris mutant are preferred conformations for apolipoprotein A-I. The salt bridge scoring indicated better energetic scoring in these alignments. The Paris (R151C) and Milano (R173C) mutants indicate a mode of change must be available. To find proper registration, one proposed change is a 'rotationally' independent circular motion of the two protein monomers about the lipid unilamellar bilayer core. Here, we present computational data for independent inter-ring rotation of the two alpha-helical monomers about the lipid unilamellar bilayer core. The simulations presented here support the existing double-belt model. We find the rotation of the two protein monomers is able to occur with biasing. We determine that a cysteine mutant at Glu107 as a possible target for future mutational studies. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling through dynamics has substantial biomedical implications.

Original languageEnglish (US)
Pages (from-to)1006-1014
Number of pages9
JournalJournal of Molecular Graphics and Modelling
Volume29
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

Fingerprint

Apolipoprotein A-I
lipids
Molecular dynamics
monomers
Monomers
molecular dynamics
proteins
Proteins
Lipid bilayers
scoring
rings
Lipids
Salts
salts
hardware description languages
Cholesterol
cysteine
cholesterol
Cysteine
Conformations

Keywords

  • Apolipoprotein A-I
  • Discoidal high density lipoprotein
  • Double belt model
  • HDL
  • Milano mutant
  • Paris mutant
  • Simulation

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Spectroscopy
  • Computer Graphics and Computer-Aided Design
  • Materials Chemistry

Cite this

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title = "Inter-ring rotation of apolipoprotein A-I protein monomers for the double-belt model using biased molecular dynamics",
abstract = "The double belt model for lipid-bound discoidal apolipoprotein A-I consists of two alpha-helical monomers bound about an unilamellar bilayer of lipids. Previous work, based on salt bridge calculations, has demonstrated that the L5/5 registration, Milano mutant, and Paris mutant are preferred conformations for apolipoprotein A-I. The salt bridge scoring indicated better energetic scoring in these alignments. The Paris (R151C) and Milano (R173C) mutants indicate a mode of change must be available. To find proper registration, one proposed change is a 'rotationally' independent circular motion of the two protein monomers about the lipid unilamellar bilayer core. Here, we present computational data for independent inter-ring rotation of the two alpha-helical monomers about the lipid unilamellar bilayer core. The simulations presented here support the existing double-belt model. We find the rotation of the two protein monomers is able to occur with biasing. We determine that a cysteine mutant at Glu107 as a possible target for future mutational studies. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling through dynamics has substantial biomedical implications.",
keywords = "Apolipoprotein A-I, Discoidal high density lipoprotein, Double belt model, HDL, Milano mutant, Paris mutant, Simulation",
author = "Thomas Caulfield",
year = "2011",
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AU - Caulfield, Thomas

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N2 - The double belt model for lipid-bound discoidal apolipoprotein A-I consists of two alpha-helical monomers bound about an unilamellar bilayer of lipids. Previous work, based on salt bridge calculations, has demonstrated that the L5/5 registration, Milano mutant, and Paris mutant are preferred conformations for apolipoprotein A-I. The salt bridge scoring indicated better energetic scoring in these alignments. The Paris (R151C) and Milano (R173C) mutants indicate a mode of change must be available. To find proper registration, one proposed change is a 'rotationally' independent circular motion of the two protein monomers about the lipid unilamellar bilayer core. Here, we present computational data for independent inter-ring rotation of the two alpha-helical monomers about the lipid unilamellar bilayer core. The simulations presented here support the existing double-belt model. We find the rotation of the two protein monomers is able to occur with biasing. We determine that a cysteine mutant at Glu107 as a possible target for future mutational studies. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling through dynamics has substantial biomedical implications.

AB - The double belt model for lipid-bound discoidal apolipoprotein A-I consists of two alpha-helical monomers bound about an unilamellar bilayer of lipids. Previous work, based on salt bridge calculations, has demonstrated that the L5/5 registration, Milano mutant, and Paris mutant are preferred conformations for apolipoprotein A-I. The salt bridge scoring indicated better energetic scoring in these alignments. The Paris (R151C) and Milano (R173C) mutants indicate a mode of change must be available. To find proper registration, one proposed change is a 'rotationally' independent circular motion of the two protein monomers about the lipid unilamellar bilayer core. Here, we present computational data for independent inter-ring rotation of the two alpha-helical monomers about the lipid unilamellar bilayer core. The simulations presented here support the existing double-belt model. We find the rotation of the two protein monomers is able to occur with biasing. We determine that a cysteine mutant at Glu107 as a possible target for future mutational studies. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling through dynamics has substantial biomedical implications.

KW - Apolipoprotein A-I

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KW - Milano mutant

KW - Paris mutant

KW - Simulation

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