Dissertations, Theses, and Capstone Projects

Date of Degree

9-2019

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biochemistry

Advisor

Rein Ulijn

Advisor

Tell Tuttle

Committee Members

Ruth Stark

Ronald Koder

Hiroshi Matsui

Subject Categories

Biochemistry | Biophysics | Materials Chemistry | Nanoscience and Nanotechnology | Physical Chemistry

Keywords

Peptides, Self-Assembly, Prebiotic Chemistry, Molecular Dynamics Simulations, Phage Display, Phase Separation

Abstract

All forms of life are based on biopolymers, which are made up of a selection of simple building blocks, such as amino acids, nucleotides, fatty acids and sugars. Their individual properties govern their interactions, giving rise to complex supramolecular structures with highly specialized functionality, including ligand recognition, catalysis and compartmentalization. In this thesis, we aim to answer the question whether short peptides could have acted as precursors of modern proteins during prebiotic evolution. Using a combination of experimental and computational techniques, we screened a large molecular search space for peptide sequences that are capable of forming supramolecular complexes with adenosine triphosphate (ATP), life’s ubiquitous energy currency, and uridine triphosphate (UTP). Our results demonstrate that peptides as short as heptamers can form dynamic supramolecular complexes, adapt their structure to a ligand upon binding, undergo phase-separation into spatially confined compartments and catalyze nucleotide-hydrolysis.

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