Assembly dynamics of two-beta sheets revealed by molecular dynamics simulations

J Chem Phys. 2009 Apr 28;130(16):164709. doi: 10.1063/1.3123532.

Abstract

The assembly dynamics of two beta sheets with different initial separation distances are explored by multiple all-atom molecular dynamics simulations with the presence of explicit water solvent. The beta sheet is composed of seven identical peptides in an antiparallel fashion. The peptide sequence is the 20-29 segment of human Islet amyloid polypeptide. Our simulations show that the assembly occurs not only in the lateral direction but also along the longitudinal direction, which provides a new insight into the assembly pathway at the early stage of fibril elongation. Based on Poisson-Boltzmann free energy analysis and quasiharmonic configuration entropy estimation, the entropic contribution is found to play an important role in the longitudinal assembly. Moreover, a possible oligomeric state with cyclic form is suggested based on one assembly model found in the simulations, illustrating the polymorphic nature of aggregation of the amyloidogenic peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / chemistry*
  • Computer Simulation
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Islet Amyloid Polypeptide
  • Models, Molecular
  • Protein Structure, Secondary
  • Thermodynamics
  • Water / chemistry*

Substances

  • Amyloid
  • Islet Amyloid Polypeptide
  • Water