Dynamical stability and assembly cooperativity of β-sheet amyloid oligomers - Effect of polarization

Yang Li, Changge Ji, Weixin Xu, John Z.H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

The soluble intermediate oligomers of amyloidogenic proteins are suspected to be more cytotoxic than the mature fibrils in neurodegenerative disorders. Here, the dynamic stability and assembly cooperativity of a model oligomer of human islet amyloid polypeptide (hIAPP) segments were explored by means of all-atom molecular dynamics (MD) simulations under different force fields including AMBER99SB, OPLS, and polarized protein-specific charge (PPC) model. Simulation results show that the dynamic stability of β-sheet oligomers is seriously impacted by electrostatic polarization. Without inclusion of polarization (simulation under standard AMBER and OPLS force field), the β-sheet oligomers are dynamically unstable during MD simulation. For comparison, simulation results under PPC give significantly more stable dynamical structures of the oligomers. Furthermore, calculation of electrostatic interaction energy between the neighboring β strands with an approximate polarizable method produces energetic evidence for cooperative assembly of β-strand oligomers. This result supports a picture of downhill-like cooperative assembly of β strands during fibrillation process. The present study demonstrates the critical role of polarization in dynamic stability and assembly cooperativity of β-sheet-rich amyloid oligomers.

Original languageEnglish (US)
Pages (from-to)13368-13373
Number of pages6
JournalJournal of Physical Chemistry B
Volume116
Issue number45
DOIs
StatePublished - Nov 15 2012

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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