Degree Name

Department

Physiology and Developmental Biology

College

Life Sciences

Defense Date

2019-03-07

Publication Date

2019-03-13

First Faculty Advisor

Steven Castle

First Faculty Reader

David Busath

Honors Coordinator

Merritt Andrus

Keywords

peptides, molecular dynamics, quantum mechanics, nmr, dehydroamino acids, anticancer

Abstract

Peptides represent a class of abundant and potent pharmaceutic compounds. Despite their appeal, the design, synthesis, and engineering of biologically relevant peptides remain a challenge. Chapter 1 introduces the various computational methods that will be used. Chapter 2 focuses on the incorporation of a special class of amino acids called bulky dehydroamino acids into the turn of β-hairpins to proteolytically stabilize peptides. Our results suggest that dehydroamino acids confer proteolytic stability by favoring a more folded state. Chapter 3 describes the structural calculations of a rare anticancer peptide called Yaku’amide using a combined molecular mechanics/quantum mechanics hybrid method. The rationale for the project is that due to several dehydroamino acids found in the structure of Yaku’amide, it is difficult to synthesize it in quantities large enough to be able to explore its biological properties. Our calculations identify two simplified versions of Yaku’amide that are easier to synthesize and retain its structure and thus likely retain its unique biological activity.