Monte Carlo studies of protein aggregation
Author
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.
Department/s
Publishing year
2012
Language
English
Pages
49-54
Publication/Series
Physics Procedia
Volume
34
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