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Molecular simulations uncover the nanomechanics of heat shock protein (70 kDa) & Indentation simulations of microtubules reveal katanin severing insights

Merz, Dale R, Jr.
http://orcid.org/0000-0001-5815-2232
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1583154342504106

Abstract Details

2020, PhD, University of Cincinnati, Arts and Sciences: Chemistry.
The nanomechanics of heat shock protein (70 kDa) and the mechanical properties of the microtubule lattice were investigated with coarse-grained molecular pulling and indentation simulations, respectively. Heat shock protein is a molecular chaperone known for its role in folding nascent peptides as they exit the ribosome and preventing protein aggregation. Preventing protein aggregation is critical for combating neuro-degenerative diseases like Alzheimer's and Parkinson’s disease. We uncovered mechanical rigidification in the substrate binding domain and lobe II of the nucleotide binding domain upon hydrolysis. We found that this rigidification was communicated allosterically and through noncontiguous residues of the protein’s subdomains contrary to the literature previously indicating the interdomain linker as the means of allosteric communication. Concerning my other areas of research, the investigations into microtubule severing by severing proteins like katanin, we discovered important mechanical properties pertinent for how microtubule severing occurs. Katanin is a severing protein expected to target microtubule lattice defects in order to induce severing. The seam was thought to be a lattice defect. Understanding how severing proteins interact with the microtubule lattice permits scientists to better understand and eventually manipulate or control cellular division. With this understanding, they can better develop and engineer pharmaceutical drugs capable of diverting, interrupting, or even accelerating the severing process. By comparing the force of indentation on and around the seam, we were able to eliminate from consideration the seam as a microtubule defect by comparing and identifying similar distributions of critical breaking forces on and off of the seam.
Ruxandra Dima, Ph.D. (Committee Chair)
Bruce Ault, Ph.D. (Committee Member)
Anna Gudmundsdottir, Ph.D. (Committee Member)
110 p.
Biophysics
heat shock protein; microtubules; molecular dynamics; pulling simulation; katanin severing; protein folding

Recommended Citations

Citations

  • Merz, Jr., D. R. (2020). Molecular simulations uncover the nanomechanics of heat shock protein (70 kDa) & Indentation simulations of microtubules reveal katanin severing insights [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1583154342504106

    APA Style (7th edition)

  • Merz, Jr., Dale. Molecular simulations uncover the nanomechanics of heat shock protein (70 kDa) & Indentation simulations of microtubules reveal katanin severing insights. 2020. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1583154342504106.

    MLA Style (8th edition)

  • Merz, Jr., Dale. "Molecular simulations uncover the nanomechanics of heat shock protein (70 kDa) & Indentation simulations of microtubules reveal katanin severing insights." Doctoral dissertation, University of Cincinnati, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1583154342504106

    Chicago Manual of Style (17th edition)

ucin1583154342504106
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This open access ETD is published by University of Cincinnati and OhioLINK.