title: Molecular events during the early stages of aggregation of GNNQQNY: An all atom MD simulation study of randomly dispersed peptides.
abstract: 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/re-associate 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.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India.
authors.forename: Alka
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India. Electronic address: balaji@iitb.ac.in.
authors.forename: Petety V
authors.initials: PV
authors.lastname: Balaji
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry*; D010455:Peptides; D066263:Protein Aggregation, Pathological / Q000378:metabolism*; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D046912:Multiprotein Complexes; D010455:Peptides
keywords: Aggregation; Amyloid; GNNQQNY; Heterogeneous; Oligomers; Polymorphism