Structural properties of amyloid β(1-40) dimer explored by replica exchange molecular dynamics simulations

Charles R. Watts, Andrew J. Gregory, Cole P. Frisbie, Sándor Lovas

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Replica exchange molecular dynamics simulations (300 ns) were used to study the dimerization of amyloid β(1-40) (Aβ(1-40)) polypeptide. Configurational entropy calculations revealed that at physiological temperature (310 K, 37°C) dynamic dimers are formed by randomly docked monomers. Free energy of binding of the two chains to each other was -93.56±6.341 kJ mol-1. Prevalence of random coil conformations was found for both chains with the exceptions of increased β-sheet content from residues 16-21 and 29-32 of chain A and residues 15-21 and 30-33 of chain B with β-turn/β-bend conformations in both chains from residues 1-16, 21-29 of chain A, 1-16, and 21-29 of chain B. There is a mixed β-turn/β-sheet region from residues 33-38 of both chains. Analysis of intra- and interchain residue distances shows that, although the individual chains are highly flexible, the dimer system stays in a loosely packed antiparallel β-sheet configuration with contacts between residues 17-21 of chain A with residues 17-21 and 31-36 of chain B as well as residues 31-36 of chain A with residues 17-21 and 31-36 of chain B. Based on dihedral principal component analysis, the antiparallel β-sheet-loop-β-sheet conformational motif is favored for many low energy sampled conformations. Our results show that Aβ(1-40) can form dynamic dimers in aqueous solution that have significant conformational flexibility and are stabilized by collapse of the central and C-terminal hydrophobic cores with the expected β-sheet-loop-β-sheet conformational motif.

Original languageEnglish (US)
JournalProteins: Structure, Function and Bioinformatics
DOIs
StateAccepted/In press - 2017

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Dimerization
Entropy
Molecular Dynamics Simulation
Principal Component Analysis
Amyloid
Dimers
Conformations
Molecular dynamics
Structural properties
Peptides
Temperature
Computer simulation
Principal component analysis
Free energy
Monomers

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Structural properties of amyloid β(1-40) dimer explored by replica exchange molecular dynamics simulations. / Watts, Charles R.; Gregory, Andrew J.; Frisbie, Cole P.; Lovas, Sándor.

In: Proteins: Structure, Function and Bioinformatics, 2017.

Research output: Contribution to journalArticle

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