Peptide Nanostructure Formation Through Self-Assembly: Computations Guide Experimental Characterization and Amino Acid Sequence Design

• Other Authors: Zimmerman, Maxwell I. (authoraut)
• Format: Others
• Language: English; English
• Published: Florida State University
• Subjects: Chemical engineering; Biomedical engineering
• Online Access: http://purl.flvc.org/fsu/fd/FSU_migr_etd-8925

The design of novel proteins with unique functions has immense application for the development of novel drugs, catalytic enzymes, vaccines, and the creation of innovative biotechnological devices. Hindering the design of novel proteins is a lack of knowledge that relates a protein amino acid sequence to its resultant structure as well as a detailed understanding of the ways in which proteins self-assemble. Analysis of peptide nanostructures may provide clues regarding self-assembly pathways and sequence-structure rules that will aid in the design of future proteins, though experimental characterization of nanostructures can often prove challenging. Here, four peptide nanostructures are analyzed using a variety of computational approaches to aid in experimental structure characterization. De novo designed peptide nanofibers RADA16-I and MAX8 are structurally characterized through comparison of experimental solid-state NMR spectra to nuclear spin simulations generated from atomic coordinates of hypothetical molecular models. The de novo designed peptide nanofiber SAF is modeled to aid in the selection of isotopically labeled residues for structure determination using solid-state NMR 2D experiments. To aid in the elucidation of toxic Aβ(1-42) oligomer structures, all-atom molecular models are generated to rationalize solid-state NMR experimental constraints. Differences between these models can be probed experimentally to refine a final structure. The structural knowledge of these peptide assemblies is then used to rationally design a pair of complementary self-assembling peptide nanofibers (CoSAN), which are analyzed in silico using molecular dynamics simulations. Synthesis and experimental characterization using circular dichroism reveal the shortcomings of the CoSAN design while raising further questions regarding self-assembly of peptides and the future of protein design. === A Thesis submitted to the Department of Chemical and Biomedical Engineering in partial fulfillment of the requirements for the degree of Master of Science. === Spring Semester, 2014. === April 17, 2014. === Computations, Modeling, Nanostructure, NMR, Peptide, Self-Assembly === Includes bibliographical references. === Anant K. Paravastu, Professor Directing Thesis; Joel R. Fried, Committee Member; Samuel C. Grant, Committee Member.