Monte Carlo studies of protein aggregation

被引：1

作者：

Jonsson, Sigurour AEgir ^{[1
]}

Staneva, Iskra ^{[1
]}

Mohanty, Sandipan ^{[2
]}

Irbaeck, Anders ^{[1
]}

机构：

[1] Lund Univ, Dept Astron & Theoret Phys, Solvegatan 14A, SE-22362 Lund, Sweden

[2] Forschungszentrum Julich, Inst Adv Simulat, Julich Supercomp Ctr, D-52425 Julich, Germany

来源：

PROCEEDINGS OF THE 25TH WORKSHOP ON COMPUTER SIMULATION STUDIES IN CONDENSED MATTER PHYSICS | 2012年 / 34卷

关键词：

protein misfolding; protein aggregation; amyloid; ALPHA-SYNUCLEIN; THERMODYNAMICS; CONFORMATION; SIMULATION; ALGORITHM; MOLECULES; PEPTIDES; OCCURS;

D O I：

10.1016/j.phpro.2012.05.008

中图分类号：

O29 [应用数学];

学科分类号：

070104 ;

摘要：

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.

引用

页码：49 / 54

页数：6

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