An Accurate Model of Polyglutamine

Publication Date

5-1-2011

Document Type

Article

Abstract

Polyglutamine repeats in proteins are highly correlated with amyloid formation and neurological disease. To better understand the molecular basis of glutamine repeat diseases, structural analysis of polyglutamine peptides as soluble monomers, oligomers, and insoluble amyloid fibrils is necessary. In this study, fluorescence resonance energy transfer (FRET) experiments and molecular dynamics simulations using different theoretical models of polyglutamine were conducted. This study demonstrates that a previously proposed simple CαCβ model of polyglutamine, denoted as FCO, accurately reproduced the present FRET results and the results of previously published FRET, triplet-state quenching, and fluorescence correlation studies. Other simple CαCβ models with random coil and extended β-strand parameters, and all-atom models with parm96 and parm99SB force fields, did not match the FRET result well. The FCO is an intrinsically disordered model with a high-effective persistence length producing extended peptides at short lengths (QN < 10). Because of an increasing number of attractive Q–Q interactions at longer lengths, the FCO model becomes increasingly more compact at lengths between QN ∼ 10–16 and is as compact as many folded proteins at QN > 16.

Publication Title

Proteins: Structure, Function, Bioinformatics

Volume

79

Issue

5

First Page

1427

Last Page

1440

DOI

10.1002/prot.22970

Publisher Policy

pre-print, post-print with embargo

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