title: Accelerating atomic-level protein simulations by flat-histogram techniques.
abstract: 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 (GIINFEQ) [corrected] 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.
authors.affiliation: Computational Biology and Biological Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund, Sweden. sigurdur.aegir@thep.lu.se
authors.forename: Sigurour A E
authors.initials: SA
authors.lastname: Jónsson
authors.forename: Sandipan
authors.initials: S
authors.lastname: Mohanty
authors.forename: Anders
authors.initials: A
authors.lastname: Irbäck
mesh_terms: D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1