Journal article
Changes to the structure and dynamics in mutations of Aβ(21-30) caused by ions in solution
The journal of physical chemistry. B, v 117(48), pp 14907-14915
05 Dec 2013
PMID: 24261958
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The structure and dynamics of the 21-30 fragment of the amyloid β-protein (Aβ(21-30)) and its Dutch [Glu22Gln], Arctic [Glu22Gly], and Iowa [Asp23Asn] isoforms are of considerable importance, as their folding may play an important role in the pathogenesis of sporadic and familial forms of Alzheimer's disease and cerebral amyloid angiopathy. A full understanding of this pathologic folding in in vivo environments is still elusive. Here we examine the interactions and effects of two neurobiologically relevant salts (CaCl2 and KCl) on the structure and dynamics of Aβ(21-30) decapeptide monomers containing the Dutch, Arctic, and Iowa charge-modifying point mutations using isobaric-isothermal (NPT) explicit water all-atom molecular-dynamics simulations. Measurements of secondary structure populations, intrapeptide hydrogen bonding, salt bridging, secondary structure lifetimes, cation-residue contacts, water-peptide hydrogen bonding, and hydration-shell water residence times reveal a variety of ion and mutation-dependent modifications to the decapeptide's structure and dynamics. In general, Ca(2+) has the effect of increasing coil-state populations and lifetimes, modifying the behavior of the decapeptide's hydration shell and diminishing intrapeptide hydrogen bonding, while K(+) is found to diminish coil populations and lifetimes and, for the case of the Iowa mutant, dramatically increase the decapeptide's propensity for β secondary structures. Mutation-dependent effects highlight the different roles of the Glu22 and Asp23 residues in either solvating or enhancing turn structures, respectively. Taken together, our results provide insights into the differential roles of different ionic species as well as specific effects on the Glu22 and Asp23 residues of Aβ(21-30) mediated by ion-decapeptide interactions and the solvent, which could be important interaction mechanisms relevant to the peptide's behavior in both in vitro and in vivo environments.
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Details
- Title
- Changes to the structure and dynamics in mutations of Aβ(21-30) caused by ions in solution
- Creators
- Micholas Dean Smith - Department of Physics, Drexel University , 3141 Chestnut Street, Philadelphia 19104, Pennsylvania, United StatesLuis Cruz
- Publication Details
- The journal of physical chemistry. B, v 117(48), pp 14907-14915
- Publisher
- American Chemical Society; Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Web of Science ID
- WOS:000328101100003
- Scopus ID
- 2-s2.0-84890089062
- Other Identifier
- 991014877686204721
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- Web of Science research areas
- Chemistry, Physical