Molecular dynamics simulation suggests possible interaction patterns at early steps of beta2-microglobulin aggregation

Biophys J. 2007 Mar 1;92(5):1673-81. doi: 10.1529/biophysj.106.098483. Epub 2006 Dec 8.

Abstract

Early events in aggregation of proteins are not easily accessible by experiments. In this work, we perform a 5-ns molecular dynamics simulation of an ensemble of 27 copies of beta(2)-microglobulin in explicit solvent. During the simulation, the formation of intermolecular contacts is observed. The simulation highlights the importance of apical residues and, in particular, of those at the N-terminus end of the molecule. The most frequently found pattern of interaction involves a head-to-head contact arrangement of molecules. Hydrophobic contacts appear to be important for the establishment of long-lived (on the simulation timescale) contacts. Although early events on the pathway to aggregation and fibril formation are not directly related to the end-state of the process, which is reached on a much longer timescale, simulation results are consistent with experimental data and in general with a parallel arrangement of intermolecular beta-strand pairs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation*
  • Models, Molecular*
  • Protein Binding
  • Protein Conformation
  • beta 2-Microglobulin / chemistry*
  • beta 2-Microglobulin / metabolism

Substances

  • beta 2-Microglobulin