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Protein Self-Assembly pp 243–262Cite as

Atomistic Simulation Tools to Study Protein Self-Aggregation

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 2039))

Abstract

Aberrant aggregation of proteins into poorly soluble, toxic structures that accumulate intracellularly or extracellularly leads to a range of disease states including Alzheimer’s, Parkinson’s, Huntington’s, prion diseases, and type II diabetes. Many of the disease-associated amyloidogenic proteins are intrinsically disordered, which makes their experimental investigation challenging due to a limited number of experimental observables to effectively characterize their ensemble of conformations. Molecular dynamics simulations provide dynamic information with atomistic detail, and are increasingly employed to study aggregation processes, offering valuable structural and mechanistic insights. In this chapter, we demonstrate the use of all-atom molecular dynamics simulations to model the self-aggregation of a six-residue amyloidogenic peptide derived from amyloid β, a 39–43 residue-long peptide associated with the pathogenesis of Alzheimer’s disease. We provide detailed instructions on how to obtain the initial monomer conformations and build the multichain systems, how to carry out the simulations, and how to analyze the simulation trajectories to investigate the peptide self-aggregation process.

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Authors and Affiliations

  1. Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada

    Deniz Meneksedag-Erol & Sarah Rauscher

  2. Department of Physics, University of Toronto, Toronto, ON, Canada

    Deniz Meneksedag-Erol & Sarah Rauscher

  3. Department of Chemistry, University of Toronto, Toronto, ON, Canada

    Sarah Rauscher

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  1. Deniz Meneksedag-Erol
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  2. Sarah Rauscher
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Correspondence to Sarah Rauscher .

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Editors and Affiliations

  1. Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland

    Jennifer J. McManus

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Meneksedag-Erol, D., Rauscher, S. (2019). Atomistic Simulation Tools to Study Protein Self-Aggregation. In: McManus, J. (eds) Protein Self-Assembly. Methods in Molecular Biology, vol 2039. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9678-0_17

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  • DOI: https://doi.org/10.1007/978-1-4939-9678-0_17

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9677-3

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