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

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 sequenc...

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Other Authors: Zimmerman, Maxwell I. (authoraut)
Format: Others
Language:English
English
Published: Florida State University
Subjects:
Online Access:http://purl.flvc.org/fsu/fd/FSU_migr_etd-8925
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spelling ndltd-fsu.edu-oai-fsu.digital.flvc.org-fsu_2535952020-06-19T03:09:23Z Peptide Nanostructure Formation Through Self-Assembly: Computations Guide Experimental Characterization and Amino Acid Sequence Design Zimmerman, Maxwell I. (authoraut) Paravastu, Anant K. (professor directing thesis) Fried, Joel R. (committee member) Grant, Samuel C. (committee member) Department of Chemical and Biomedical Engineering (degree granting department) Florida State University (degree granting institution) Text text Florida State University Florida State University English eng 1 online resource computer application/pdf 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. Chemical engineering Biomedical engineering FSU_migr_etd-8925 http://purl.flvc.org/fsu/fd/FSU_migr_etd-8925 This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them. http://diginole.lib.fsu.edu/islandora/object/fsu%3A253595/datastream/TN/view/Peptide%20Nanostructure%20Formation%20Through%20Self-Assembly.jpg
collection NDLTD
language English
English
format Others
sources NDLTD
topic Chemical engineering
Biomedical engineering
spellingShingle Chemical engineering
Biomedical engineering
Peptide Nanostructure Formation Through Self-Assembly: Computations Guide Experimental Characterization and Amino Acid Sequence Design
description 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.
author2 Zimmerman, Maxwell I. (authoraut)
author_facet Zimmerman, Maxwell I. (authoraut)
title Peptide Nanostructure Formation Through Self-Assembly: Computations Guide Experimental Characterization and Amino Acid Sequence Design
title_short Peptide Nanostructure Formation Through Self-Assembly: Computations Guide Experimental Characterization and Amino Acid Sequence Design
title_full Peptide Nanostructure Formation Through Self-Assembly: Computations Guide Experimental Characterization and Amino Acid Sequence Design
title_fullStr Peptide Nanostructure Formation Through Self-Assembly: Computations Guide Experimental Characterization and Amino Acid Sequence Design
title_full_unstemmed Peptide Nanostructure Formation Through Self-Assembly: Computations Guide Experimental Characterization and Amino Acid Sequence Design
title_sort peptide nanostructure formation through self-assembly: computations guide experimental characterization and amino acid sequence design
publisher Florida State University
url http://purl.flvc.org/fsu/fd/FSU_migr_etd-8925
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