Accelerating atomic-level protein simulations by flat-histogram techniques.

Research output: Contribution to journalArticle


Flat-histogram techniques provide a powerful approach to the simulation of first-order-like phase transitions and are potentially very useful for protein studies. Here, we test this approach by implicit solvent all-atom Monte Carlo (MC) simulations of peptide aggregation, for a 7-residue fragment (GIIFNEQ) of the Cu/Zn superoxide dismutase 1 protein (SOD1). In simulations with 8 chains, we observe two distinct aggregated/non-aggregated phases. At the midpoint temperature, these phases coexist, separated by a free-energy barrier of height 2.7 k(B)T. We show that this system can be successfully studied by carefully implemented flat-histogram techniques. The frequency of barrier crossing, which is low in conventional canonical simulations, can be increased by turning to a two-step procedure based on the Wang-Landau and multicanonical algorithms.


External organisations
  • Jülich Research Centre
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biophysics
Original languageEnglish
Article number125102
JournalJournal of Chemical Physics
Issue number12
Publication statusPublished - 2011
Publication categoryResearch