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

Summary, in English

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.

• Author: Sigurdur Jonsson; Sandipan Mohanty; Anders Irbäck
• Department/s: Computational Biology and Biological Physics - Has been reorganised; MultiPark: Multidisciplinary research focused on Parkinson´s disease
• Publishing year: 2011
• Language: English
• Publication/Series: Journal of Chemical Physics
• Volume: 135
• Issue: 12
• Links: http://dx.doi.org/10.1063/1.3643328
• Document type: Journal article
• Publisher: American Institute of Physics (AIP)
• Topic: Biophysics
• Status: Published
• ISBN/ISSN/Other: ISSN: 0021-9606