Curtin University Homepage
  • Library
  • FAQ
    • Log in

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    Computational study of aggregation mechanism in human lysozyme[D67H]

    Access Status
    Open access via publisher
    Authors
    Patel, Dharmeshkumar
    Kuyucak, S.
    Date
    2017
    Collection
    • Curtin Research Publications
    Type
    Journal Article
    Metadata
    Show full item record
    Abstract

    © 2017 Patel, Kuyucak. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Aggregation of proteins is an undesired phenomena that affects both human health and bioengineered products such as therapeutic proteins. Finding preventative measures could be facilitated by a molecular-level understanding of dimer formation, which is the first step in aggregation. Here we present a molecular dynamics (MD) study of dimer formation propensity in human lysozyme and its D67H variant. Because the latter protein aggregates while the former does not, they offer an ideal system for testing the feasibility of the proposed MD approach which comprises three stages: i) partially unfolded conformers involved in dimmer formation are generated via high-temperature MD simulations, ii) potential dimer structures are searched using docking and refined with MD, iii) free energy calculations are performed to find the most stable dimer structure. Our results provide a detailed explanation for how a single mutation (D67H) turns human lysozyme from non-aggregating to an aggregating protein. Conversely, the proposed method can be used to identify the residues causing aggregation in a protein, which can be mutated to prevent it.

    Citation
    Patel, D. and Kuyucak, S. 2017. Computational study of aggregation mechanism in human lysozyme[D67H]. PLoS ONE. 12 (5).
    Source Title
    PLoS ONE
    URI
    http://hdl.handle.net/20.500.11937/63045
    DOI
    10.1371/journal.pone.0176886
    Department
    School of Pharmacy and Biomedical Sciences

    Related items

    Showing items related by title, author, creator and subject.

    • A potential new, stable state of the E-cadherin strand-swapped dimer in solution
      Schumann-Gillett, A.; Mark, A.; Deplazes, Evelyne; O'Mara, M. (2017)
      E-cadherin is a transmembrane glycoprotein that facilitates inter-cellular adhesion in the epithelium. The ectodomain of the native structure is comprised of five repeated immunoglobulin-like domains. All E-cadherin crystal ...
    • The potential of a cross-linked human serum albumin dimer in diabetic rats as an augmenting agent for antidiabetic drugs
      Taguchi, K.; Chuang, Victor; Yamasaki, K.; Kawai, K.; Maruyama, T.; Komatsu, T.; Otagiri, Masaki (2015)
      Purpose: The half-life of insulin analogs and glucagon like peptide-1 (GLP-1) receptor agonist is prolonged through binding to albumin, but this may not occur in hypoalbuminemic diabetic patients with protein leaking from ...
    • S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes
      Kinoshita, R.; Ishima, Y.; Ikeda, M.; Kragh-Hansen, U.; Fang, J.; Nakamura, H.; Chuang, Victor; Tanaka, R.; Maeda, H.; Kodama, A.; Watanabe, H.; Maeda, H.; Otagiri, M.; Maruyama, T. (2015)
      © 2015 Elsevier B.V. All rights reserved. The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors, and it can serve as a basis for the development of macromolecular anticancer therapy. ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorsTitlesSubjectsDocument TypesThis CollectionIssue DateAuthorsTitlesSubjectsDocument Types

    My Account

    Log in

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Connect with Curtin

    • 
    • 
    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Send FeedbackContact Us
    DSpace software copyright © 2002-2015  DuraSpace