Sequence effects on the conformational properties of the amyloid beta (1-28) peptide: testing a proposed mechanism for the alpha-->beta transition.

Abstract:

:Molecular dynamics simulations have been used to successfully reproduce the observed pH-dependent conformational properties of the amyloid beta(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.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Kirshenbaum K,Daggett V

doi

10.1021/bi00023a010

subject

Has Abstract

pub_date

1995-06-13 00:00:00

pages

7640-7

issue

23

eissn

0006-2960

issn

1520-4995

journal_volume

34

pub_type

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