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Monte Carlo studies of protein aggregation

Jonsson, Sigurdur LU ; Staneva, Iskra LU ; Mohanty, Sandipan LU and Irbäck, Anders LU (2012) 25th Workshop on Computer Simulation Studies in Condensed Matter Physics In Physics Procedia 34. p.49-54
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
protein misfolding, protein aggregation, amyloid
in
Physics Procedia
volume
34
pages
49 - 54
publisher
Elsevier
conference name
25th Workshop on Computer Simulation Studies in Condensed Matter Physics
external identifiers
  • wos:000314152800008
  • scopus:85013130546
ISSN
1875-3892
DOI
10.1016/j.phpro.2012.05.008
language
English
LU publication?
yes
id
ef5cf631-98d0-423f-a82a-cf81fb3d43f9 (old id 3577806)
date added to LUP
2013-03-20 15:18:46
date last changed
2017-10-01 04:00:12
@inproceedings{ef5cf631-98d0-423f-a82a-cf81fb3d43f9,
  abstract     = {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       = {Jonsson, Sigurdur and Staneva, Iskra and Mohanty, Sandipan and Irbäck, Anders},
  booktitle    = {Physics Procedia},
  issn         = {1875-3892},
  keyword      = {protein misfolding,protein aggregation,amyloid},
  language     = {eng},
  pages        = {49--54},
  publisher    = {Elsevier},
  title        = {Monte Carlo studies of protein aggregation},
  url          = {http://dx.doi.org/10.1016/j.phpro.2012.05.008},
  volume       = {34},
  year         = {2012},
}