The beta-strand-loop-beta-strand conformation is marginally populated in beta2-microglobulin (20-41) peptide in solution as revealed by replica exchange molecular dynamics simulations

Biophys J. 2008 Jul;95(2):510-7. doi: 10.1529/biophysj.107.125054. Epub 2008 Apr 11.

Abstract

Solid-state NMR study shows that the 22-residue K3 peptide (Ser(20)-Lys(41)) from beta(2)-microglobulin (beta(2)m) adopts a beta-strand-loop-beta-strand conformation in its fibril state. Residue Pro(32) has a trans conformation in the fibril state of the peptide, while it adopts a cis conformation in the native state of full-length beta(2)m. To get insights into the structural properties of the K3 peptide, and determine whether the strand-loop-strand conformation is encoded at the monomeric level, we run all-atom explicit solvent replica exchange molecular dynamics on both the cis and trans variants. Our simulations show that the conformational space of the trans- and cis-K3 peptides is very different, with 1% of the sampled conformations in common at room temperature. In addition, both variants display only 0.3-0.5% of the conformations with beta-strand-loop-beta-strand character. This finding, compared to results on the Alzheimer's Abeta peptide, suggests that the biases toward aggregation leading to the beta-strand-loop-beta-strand conformation in fibrils are peptide-dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Models, Chemical*
  • Models, Molecular*
  • Peptides / chemistry
  • Protein Conformation
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / ultrastructure*
  • Solutions
  • beta 2-Microglobulin / chemistry*
  • beta 2-Microglobulin / ultrastructure*

Substances

  • Peptides
  • Proteins
  • Solutions
  • beta 2-Microglobulin