Curtin University Homepage
  • Library
  • Help
    • Admin

    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

    Combination of Ambiguous and Unambiguous Data in the Restraint-driven Docking of Flexible Peptides with HADDOCK: The Binding of the Spider Toxin PcTx1 to the Acid Sensing Ion Channel (ASIC) 1a

    Access Status
    Fulltext not available
    Authors
    Deplazes, Evelyne
    Davies, J.
    Bonvin, A.
    King, G.
    Mark, A.
    Date
    2016
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Deplazes, E. and Davies, J. and Bonvin, A. and King, G. and Mark, A. 2016. Combination of Ambiguous and Unambiguous Data in the Restraint-driven Docking of Flexible Peptides with HADDOCK: The Binding of the Spider Toxin PcTx1 to the Acid Sensing Ion Channel (ASIC) 1a. Journal of Chemical Information and Modeling. 56 (1): pp. 127-138.
    Source Title
    Journal of Chemical Information and Modeling
    DOI
    10.1021/acs.jcim.5b00529
    ISSN
    1549-9596
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/13339
    Collection
    • Curtin Research Publications
    Abstract

    Peptides that bind to ion channels have attracted much interest as potential lead molecules for the development of new drugs and insecticides. However, the structure determination of large peptide-channel complexes using experimental methods is challenging. Thus structural models are often derived from combining experimental information with restraint-driven docking approaches. Using the complex formed by the venom peptide PcTx1 and the acid sensing ion channel (ASIC) 1a as a case study, we have examined the effect of different combinations of restraints and input structures on the statistical likelihood of (a) correctly predicting the structure of the binding interface and (b) the ability to predict which residues are involved in specific pairwise peptide-channel interactions. For this, we have analyzed over 200 000 water-refined docked structures obtained with various amounts and types of restraints of the peptide-channel complex predicted using the docking program HADDOCK. We found that increasing the number of restraints or even the use of pairwise interaction data resulted in only a modest improvement in the likelihood of finding a structure within a given accuracy. This suggests that shape complementarity and the force field make a large contribution to the accuracy of the predicted structure. The results also showed that there are large variations in the accuracy of the predicted structure depending on the precise combination of residues used as restraints. Finally, we reflect on the limitations of relying on geometric criteria such as root-mean square deviations to assess the accuracy of docking procedures. We propose that in addition to currently used measures, the likelihood of finding a structure within a given level of accuracy should be also used to evaluate docking methods.

    Related items

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

    • Optimization of protein-protein docking for predicting Fc-protein interactions
      Agostino, Mark; Mancera, R.; Ramsland, P.; Fernández-Recio, J. (2016)
      The antibody crystallizable fragment (Fc) is recognized by effector proteins as part of the immune system. Pathogens produce proteins that bind Fc in order to subvert or evade the immune response. The structural ...
    • Molecular dynamics and functional studies define a hot spot of crystal contacts essential for PcTx1 inhibition of acid-sensing ion channel 1a
      Saez, N.; Deplazes, Evelyne; Cristofori-Armstrong, B.; Chassagnon, I.; Lin, X.; Mobli, M.; Mark, A.; Rash, L.; King, G. (2015)
      Background and Purpose: The spider-venom peptide PcTx1 is the most potent and selective inhibitor of acid-sensing ion channel (ASIC) 1a. It has centrally acting analgesic activity and is neuroprotective in rodent models ...
    • Non-canonical anchor motif peptides bound to MHC class I induce cellular responses
      Lazoura, E.; Lodding, J.; Farrugia, W.; Day, S.; Ramsland, Paul; Apostolopoulos, V. (2009)
      The major histocompatibility complex (MHC) on the surface of antigen presenting cells functions to display peptides to the T cell receptor (TCR). Recognition of peptide-MHC by T cells initiates a cascade of signals, which ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

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

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.