• Login
    View Item 
    •   DSpace@RPI Home
    • Rensselaer Libraries
    • RPI Theses Online (Complete)
    • View Item
    •   DSpace@RPI Home
    • Rensselaer Libraries
    • RPI Theses Online (Complete)
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Determination of thermodynamic and kinetic properties of proteins from atomistic computer simulations

    Author
    Jiménez Cruz, Camilo Andrés
    View/Open
    170142_JimenezCruz_rpi_0185E_10198.pdf (26.12Mb)
    Other Contributors
    García, Angel E.; Giedt, Joel; Meunier, Vincent; Garde, Shekhar; Makhatadze, George I.;
    Date Issued
    2013-08
    Subject
    Physics
    Degree
    PhD;
    Terms of Use
    This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.;
    Metadata
    Show full item record
    URI
    https://hdl.handle.net/20.500.13015/981
    Abstract
    Proteins undergo fluctuations spanning a wide range of timescales. Atom oscillations and bond vibration happen in femtoseconds, while the timescales of non-local contacts and domain rearrangements range from miliseconds to seconds to occur. As a result of this hierarchy of processes, protein folding is a rare event, and thus, the dwelling times in local metastable states are much longer than the transition times between such states. Since the function of proteins is determined by their atomic motions, a detailed understanding of protein folding can result in significant advances in biology and medicine. Molecular Dynamics (MD) simulations of biomolecular systems, based on physical models of the interactions, provide atomic-level description of these processes. While MD directly samples temporal and spatial resolutions not available to experiments, it presents new challenges in the generation, validation and analysis of datasets. In this thesis, we focus on the characterization of folding/unfolding equilibrium and kinetic properties of a beta hairpin and globular mini protein. We use extensive all-atom, explicit solvent, Replica Exchange Molecular Dynamics (REMD) simulations, to generate the equilibrium ensemble of configurations of the systems studied and selected mutants. Our results high- light the importance of non-native interactions in the relative stability of the folded state. Kinetic networks for the systems were generated by constructing Markov State Models (MSMs), using thousands of independent MD simulations. We provide new approaches to solve some of the challenges of building MSMs. Specifically, we develop novel strategies for the discretization of the configurational space, and apply them to the model systems.;
    Description
    August 2013; School of Science
    Department
    Dept. of Physics, Applied Physics, and Astronomy;
    Publisher
    Rensselaer Polytechnic Institute, Troy, NY
    Relationships
    Rensselaer Theses and Dissertations Online Collection;
    Access
    Restricted to current Rensselaer faculty, staff and students. Access inquiries may be directed to the Rensselaer Libraries.;
    Collections
    • RPI Theses Online (Complete)

    Browse

    All of DSpace@RPICommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Login

    DSpace software copyright © 2002-2022  DuraSpace
    Contact Us | Send Feedback
    DSpace Express is a service operated by 
    Atmire NV