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Molecular events during the early stages of aggregation of GNNQQNY: An all atom MD simulation study of randomly dispersed peptides

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Title Molecular events during the early stages of aggregation of GNNQQNY: An all atom MD simulation study of randomly dispersed peptides
 
Creator SRIVASTAVA, A
BALAJI, PV
 
Subject AMYLOID-FORMING PEPTIDE
YEAST PRION SUP35
CROSS-BETA-SPINE
DYNAMICS SIMULATIONS
PROTEIN AGGREGATION
MISFOLDING DISEASES
SECONDARY STRUCTURE
FIBRIL FORMATION
ALPHA-SYNUCLEIN
EXPLICIT WATER
Amyloid
Oligomers
Aggregation
GNNQQNY
Polymorphism
Heterogeneous
 
Description This study probes the early events during lag phase of aggregation of GNNQQNY using all atom MD simulations in explicit solvent. Simulations were performed by varying system size, temperature and starting configuration. Peptides dispersed randomly in the simulation box come together early on in the simulation and form aggregates. These aggregates are dynamic implying the absence of stabilizing interactions. This facilitates the exploration of alternate arrangements. The constituent peptides sample a variety of conformations, frequently re-orient and re-arrange with respect to each other and dissociate from/reassociate with the aggregate. The size and lifetime of aggregates vary depending upon the number of inter-peptide backbone H-bonds. Most of the aggregates formed are amorphous but crystalline aggregates of smaller size (mainly 2-mers) do appear and sustain for varying durations of time. The peptides in crystalline 2-mers are mostly anti-parallel. The largest crystalline aggregate that appears is a 4-mer in a single sheet and a 4-, 5-, or 6-mer in double layered arrangement. Crystalline aggregates grow either by the sequential addition of peptides, or by the head-on or lateral collision-adhesion of 2-mers. The formation of various smaller aggregates suggests the polymorphic nature of oligomers and heterogeneity in the lag phase. (C) 2015 Elsevier Inc. All rights reserved.
 
Publisher ACADEMIC PRESS INC ELSEVIER SCIENCE
 
Date 2016-01-15T04:29:09Z
2016-01-15T04:29:09Z
2015
 
Type Article
 
Identifier JOURNAL OF STRUCTURAL BIOLOGY, 192(3)376-391
1047-8477
1095-8657
http://dx.doi.org/10.1016/j.jsb.2015.09.020
http://dspace.library.iitb.ac.in/jspui/handle/100/17759
 
Language en