Electrostatic Polarization Effect on Cooperative Aggregation of Full Length Human Islet Amyloid

Yang Li, Xianwei Wang, Longlong Ren, Xuecheng Cao, Changge Ji, Fei Xia, John Z.H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Amyloid aggregation initiates from a slow nucleation process, where the association of monomers is unfavorable in energetics. In principle, the enthalpy change for aggregation should compensate the entropy loss as new monomers attach to formed oligomers. However, the classical force fields with fixed point charges failed to yield the correct enthalpy change due to the lack of electrostatic polarization effect on amyloid aggregation. In this work, we performed molecular dynamics simulation for the full-length human islet amyloid using the polarized protein-specific charges and calculated the electrostatic interaction energy for amyloid oligomers. The results of molecular dynamics simulation show that the aggregates simulated with polarized charges have larger enthalpy change than that with fixed charges. The large enthalpy change mainly originates from the electrostatic polarization, which makes a significant contribution to the cooperative effect of aggregation and facilitates the nucleation process of amyloids.

Original languageEnglish (US)
Pages (from-to)1587-1595
Number of pages9
JournalJournal of Chemical Information and Modeling
Volume58
Issue number8
DOIs
StatePublished - Aug 27 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences

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