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Distinct phases of free α‐synuclein—A Monte Carlo study
Author(s) -
Jónsson Sigurður Ægir,
Mohanty Sandipan,
Irbäck Anders
Publication year - 2012
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24107
Subject(s) - monomer , tetramer , monte carlo method , crystallography , fibril , chemical physics , phase (matter) , chemistry , molecular dynamics , materials science , statistical physics , physics , computational chemistry , mathematics , biochemistry , statistics , organic chemistry , enzyme , polymer
The α‐synuclein protein (αS), implicated in Parkinson's disease, shows conformational versatility. It aggregates into β‐sheet‐rich fibrils, occurs in helical membrane‐bound forms, is disordered as a free monomer, and has recently been suggested to have a folded helical tetramer as its main physiological form. Here, we use implicit solvent all‐atom Monte Carlo methods to explore the conformational ensemble sampled by the free αS monomer. We analyze secondary structure propensities, size, and topological properties and compare with existing experimental data. Our study suggests that free αS has two distinct phases. One phase has the expected disordered character. The other phase also shows large conformational variability. However, in this phase, the β‐strand content is substantial, and the backbone fold shows statistical similarities with that in αS fibrils. Presence of this phase is consistent with data from low‐temperature experiments. Conversion of disordered αS to this fibril‐like form requires the crossing of a rather large apparent free‐energy barrier. Proteins © 2012 Wiley Periodicals, Inc.