• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Development of Additive and Polarizable Force Field Parameters for Polypeptides

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Zhu_umaryland_0373D_10337.pdf
    Size:
    16.01Mb
    Format:
    PDF
    Download
    Author
    Zhu, Xiao
    Advisor
    MacKerell, Alexander D., Jr.
    Date
    2012
    
    Metadata
    Show full item record
    Abstract
    Simulations of biological macromolecules are continually improving due to the extension and continued optimization of empirical force fields based on molecular mechanics. The quality of this "balls-on-springs" model is likely to increase, though limited by the nature of molecular mechanics, as more experimental data become available allowing for further optimization of the underlying parameters. Classically, force fields employed a fixed-charge, or additive, scheme where partial atomic charges on atoms cannot change during a simulation such that changes in molecular dipole (i.e. explicit polarization) as a function of environment are lost. Here, we describe the development, optimization, and application of a polarizable CHARMM force field that explicitly accounts for molecular polarizability via the inclusion of atomic polarizability based on the classical Drude oscillator. We begin by presenting an overview of the history of the CHARMM empirical force field, its various components, applications, as well as the formalisms for the inclusion of polarizability in force fields. This is followed by development efforts as part of this thesis towards the completion of the polarizable force field for simulations of protein. In Chapter 3, a systematic study of the side-chain conformations was performed using quantum mechanical methods. Through comparisons with a large-scale survey of the protein crystal structures, a relationship was drawn between the intrinsic energetics and occurrences in protein structures. The intrinsic energetics were then used as target data for the optimization of side-chain torsion parameters, as discussed in Chapter 4; the data and optimization approach is likely to be of value to other empirical force field development communities. Because one of the advantages of the polarizable force field is more accurate description of the electrostatics, the performance of the force field in the calculation of pKas was undertaken. In Chapter 5 we present data for the development of parameters for alternative protonation states of the Cys, Lys, and Tyr side-chains, opening doors to simulations of these species within protein systems. Finally, in Chapter 6 we applied the polarizable force field in the calculation of pKas for select residues in RNase A, demonstrating the advantages and potential challenges with respect to future optimization of the Drude polarizable force field.
    Description
    University of Maryland, Baltimore. Pharmaceutical Sciences. Ph.D. 2012
    Keyword
    CHARMM
    force field
    molecular dynamics
    polarizable
    simulation
    Molecular Dynamics Simulation
    Proteins
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/2157
    Collections
    Theses and Dissertations All Schools
    Theses and Dissertations School of Pharmacy

    entitlement

     
    DSpace software (copyright © 2002 - 2019)  DuraSpace
    Quick Guide | Policies | Contact Us
    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.