• Login
    View Item 
    •   Home
    • Faculty/ Researcher Works
    • Faculty/ Researcher Works
    • View Item
    •   Home
    • Faculty/ Researcher Works
    • Faculty/ Researcher Works
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of TUScholarShareCommunitiesDateAuthorsTitlesSubjectsGenresThis CollectionDateAuthorsTitlesSubjectsGenres

    My Account

    LoginRegister

    Help

    AboutPoliciesHelp for DepositorsData DepositFAQs

    Statistics

    Display statistics

    Correlated Electrostatic Mutations Provide a Reservoir of Stability in HIV Protease

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Correlated electrostatic mutations ...
    Size:
    1.110Mb
    Format:
    PDF
    Download
    Genre
    Journal Article
    Date
    2012-09-01
    Author
    Haq, O
    Andrec, M
    Morozov, AV
    Levy, RM
    Subject
    Amino Acid Sequence
    Computer Simulation
    Enzyme Stability
    HIV Protease
    Models, Chemical
    Models, Genetic
    Models, Molecular
    Molecular Sequence Data
    Mutation
    Static Electricity
    Statistics as Topic
    Structure-Activity Relationship
    Show allShow less
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/5450
    
    Metadata
    Show full item record
    DOI
    10.1371/journal.pcbi.1002675
    Abstract
    HIV protease, an aspartyl protease crucial to the life cycle of HIV, is the target of many drug development programs. Though many protease inhibitors are on the market, protease eventually evades these drugs by mutating at a rapid pace and building drug resistance. The drug resistance mutations, called primary mutations, are often destabilizing to the enzyme and this loss of stability has to be compensated for. Using a coarse-grained biophysical energy model together with statistical inference methods, we observe that accessory mutations of charged residues increase protein stability, playing a key role in compensating for destabilizing primary drug resistance mutations. Increased stability is intimately related to correlations between electrostatic mutations - uncorrelated mutations would strongly destabilize the enzyme. Additionally, statistical modeling indicates that the network of correlated electrostatic mutations has a simple topology and has evolved to minimize frustrated interactions. The model's statistical coupling parameters reflect this lack of frustration and strongly distinguish like-charge electrostatic interactions from unlike-charge interactions for ≈90% of the most significantly correlated double mutants. Finally, we demonstrate that our model has considerable predictive power and can be used to predict complex mutation patterns, that have not yet been observed due to finite sample size effects, and which are likely to exist within the larger patient population whose virus has not yet been sequenced. © 2012 Haq et al.
    Citation to related work
    Public Library of Science (PLoS)
    Has part
    PLoS Computational Biology
    ADA compliance
    For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
    ae974a485f413a2113503eed53cd6c53
    http://dx.doi.org/10.34944/dspace/5432
    Scopus Count
    Collections
    Faculty/ Researcher Works

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Temple University Libraries | 1900 N. 13th Street | Philadelphia, PA 19122
    (215) 204-8212 | scholarshare@temple.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.