Sequence effects on the conformational properties of the amyloid β(1-28) peptide: Testing a proposed mechanism for the α → β transition

Kent Kirshenbaum, Valerie Daggett

Research output: Contribution to journalArticle

Abstract

Molecular dynamics simulations have been used to successfully reproduce the observed pH-dependent conformational properties of the amyloid β(1-28) peptide [Kirshenbaum and Daggett (1995) Biochemistry, 34, 7629-7639]. On the basis of these simulations a mechanism was proposed for the unfolding of the N-terminal portion of the peptide at neutral pH when beginning from the helical conformation. It was proposed that interactions between the side chains of Ser 8 and Glu 11 are important in determining the pH dependence of the helix content. Here we further investigate this proposed mechanism and the residues involved in the conformational transition by performing computational "mutagenesis" studies. On the basis of simulations of the mutant peptides, the importance of the Ser 8-Glu 11 interaction is substantiated, and further details of the conformational transition are elucidated.

Original languageEnglish (US)
Pages (from-to)7640-7647
Number of pages8
JournalBiochemistry
Volume34
Issue number23
StatePublished - 1995

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Amyloid
Peptides
Testing
Mutagenesis
Biochemistry
Molecular Dynamics Simulation
Conformations
Molecular dynamics
Computer simulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sequence effects on the conformational properties of the amyloid β(1-28) peptide : Testing a proposed mechanism for the α → β transition. / Kirshenbaum, Kent; Daggett, Valerie.

In: Biochemistry, Vol. 34, No. 23, 1995, p. 7640-7647.

Research output: Contribution to journalArticle

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