Tyler Smith

Bound Volume Number

Volume II

Degree Type

Honors Capstone Project

Date of Submission

Spring 5-2016

Capstone Advisor

Ivan Korendovych

Capstone Major

Biomedical and Chemical Engineering

Capstone College

Arts and Science

Audio/Visual Component



Proteins, de novo, three- dimensional structures

Capstone Prize Winner


Won Capstone Funding


Honors Categories

Sciences and Engineering

Subject Categories



Proteins carry out many extremely efficient functions, including catalysis and biomolecule recognition. Underlying this efficiency is their extraordinary complexity and ability to fold into unique three-dimensional structures. Attempts to replicate this efficiency through de novo design have only shown moderate success, and it is unclear how modern-day proteins may have evolved. However, short peptides that alternate hydrophobic and hydrophilic residues can self-assemble into amyloid fibrils to achieve well-defined secondary structure. These aggregates may have served as a template from which the first proteins were derived. We designed self-assembling seven-residue peptides that are able to act as Zn2+-dependent esterases. Zn2+ acts to both help induce fibril formation and to serve as a metal cofactor to catalyze acyl ester hydrolysis. Furthermore, we developed a second set of peptides to recognize a target molecule with moderate specificity. The ability of this simple system to catalyze a chemical reaction and exhibit biomolecule recognition suggests that similar peptide aggregates may have been evolutionary precursors to modern-day proteins. Additionally, the ability to use a minimalistic design approach to generate functional fibrils could have implications for the development of simple nanostructured biomaterials. By using an alternating hydrophobic/hydrophilic template, novel functionality can be introduced into simple peptide aggregates.

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

Included in

Biochemistry Commons



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