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Structure and Dynamics of Supramolecular Aggregate Studied Using Molecular Dynamics Simulations: Protein Adsorption at Solid Surfaces and NMR Cross Relaxation in Nonionic Micelles

Talley Edwards, Allison
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553613189008144

Abstract Details

2019, PhD, University of Cincinnati, Arts and Sciences: Chemistry.
The physical properties of surfactant and amphiphile aggregate structures, for example folded globular proteins or surfactant solutions, are strongly modulated by changes in their aqueous environment such as solvated molecules, ions or solid substrates. The ability to study at a molecular level the structure and dynamics in these systems can aid in understanding the origin of many important properties and interactions ranging from medical implant biofouling to the activity of enzymatic scaffolds to the viscosity and stability of formulated soaps and detergents. To that end, I address two issues pertaining to these types of problems in this dissertation. In part I of this thesis, I use coarse-grained implicit solvent Langevin dynamics simulations to probe the unfolding of three protein fold motifs: an all-alpha four-helix bundle, a four strand beta barrel, and a mixed fold alpha/beta structure. These three protein folds are then placed near three hydrophobic surfaces: a planar hexagonal graphene-like structure and two curved hexagonal carbon nanotube-like surfaces. For the curved surfaces the radii of the tubes are created either with a relatively large or small radius and placed in a linear arrangement resulting in deep or shallow grooves. The proteins are initially oriented in several rotational states for each surface. My results indicate that binding and unfolding occur by different mechanisms depending on both the protein fold, its original orientation with respect to the surface and the topological character of the surface. Specifically, all-alpha four-helix bundle and the four strand beta barrel have competing stability profiles, where the four-helix bundle is more stable in the presence of curved surfaces and the beta barrel is stabilized in planar environments. This led to an interesting result with the alpha/beta fold, where the surface topology and initial orientation of the protein led to stable partially folded states following the trends found in the four helix bundle and beta barrel. In part II of the thesis, I investigate micelle morphology utilizing nuclear magnetic resonance spectroscopy (NMR). Here I measure changes in nuclear Overhauser effect (2D NOESY) cross peaks of nonionic surfactants as a function of micelle shape. I found I am able to systematically change the sign of the cross peak from positive to negative between the protons located at the hydrophobic/hydrophilic boundary of the micelle. This sign inversion can be induced with thermal or compositional changes in the micelle system that corresponds to transitions between spherical or cylindrical micelles. While the NMR data appears to be very sensitive to micelle shape (as indicated by SANS and known standard phase diagrams of the micelle systems) a molecular mechanism for the cross peak sign change is not readily apparent. To address this I use atomistic explicit solvent simulations of the compositional micelle system, where the simulated micelle shapes were determined experimentally by SANS collected on the NMR samples and previous literature suggestions. The results indicate that the change in NOE cross peak sign is due to differences in intermolecular interactions that arise due to the packing of the molecules.
George Stan, Ph.D. (Committee Chair)
Thomas Beck, Ph.D. (Committee Member)
Charles Eads, PhD (Committee Member)
Anna Gudmundsdottir, Ph.D. (Committee Member)
116 p.
Physical Chemistry
Amphiphilie aggregate; Surface-Protein Interactions; Molecular Dynamics Simulations; NMR; NOESY

Recommended Citations

Citations

  • Talley Edwards, A. (2019). Structure and Dynamics of Supramolecular Aggregate Studied Using Molecular Dynamics Simulations: Protein Adsorption at Solid Surfaces and NMR Cross Relaxation in Nonionic Micelles [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553613189008144

    APA Style (7th edition)

  • Talley Edwards, Allison. Structure and Dynamics of Supramolecular Aggregate Studied Using Molecular Dynamics Simulations: Protein Adsorption at Solid Surfaces and NMR Cross Relaxation in Nonionic Micelles. 2019. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553613189008144.

    MLA Style (8th edition)

  • Talley Edwards, Allison. "Structure and Dynamics of Supramolecular Aggregate Studied Using Molecular Dynamics Simulations: Protein Adsorption at Solid Surfaces and NMR Cross Relaxation in Nonionic Micelles." Doctoral dissertation, University of Cincinnati, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553613189008144

    Chicago Manual of Style (17th edition)

ucin1553613189008144
152
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This open access ETD is published by University of Cincinnati and OhioLINK.