Monte Carlo studies of protein aggregation

Summary, in English

The disease-linked amyloid beta (A beta) and alpha-synuclein (alpha S) proteins are both fibril-forming and natively unfolded in free monomeric form. Here, we discuss two recent studies, where we used extensive implicit solvent all-atom Monte Carlo (MC) simulations to elucidate the conformational ensembles sampled by these proteins. For alpha S, we somewhat unexpectedly observed two distinct phases, separated by a clear free-energy barrier. The presence of the barrier makes alpha S, with 140 residues, a challenge to simulate. By using a two-step simulation procedure based on flat-histogram techniques, it was possible to alleviate this problem. The barrier may in part explain why fibril formation is much slower for alpha S than it is for A beta.

• Author: Sigurdur Jonsson; Iskra Staneva; Sandipan Mohanty; Anders Irbäck
• Department/s: Computational Biology and Biological Physics - Undergoing reorganization; Theoretical Particle Physics - Undergoing reorganization
• Publishing year: 2012
• Language: English
• Pages: 49-54
• Publication/Series: Physics Procedia
• Volume: 34
• Links: http://dx.doi.org/10.1016/j.phpro.2012.05.008
• Document type: Conference paper
• Publisher: Elsevier
• Topic: Subatomic Physics; Biophysics
• Keywords: protein misfolding; protein aggregation; amyloid
• Conference name: 25th Workshop on Computer Simulation Studies in Condensed Matter Physics
• Conference date: 2012-02-20 - 2012-02-24
• Status: Published
• ISBN/ISSN/Other: ISSN: 1875-3892