Zanyah Shepherd

Zanyah Shepherd

Biography

Zanyah Shepherd is a rising sophomore chemistry major at Claflin University. Born inSoutheast, DC, and raised in Temple Hills, MD, she was surrounded by family members in the medical field, sparking her appreciation for healthcare. After a computational bioinformatics internship at Howard University focused on protein stability and its role in diseases like cancer, Zanyah realized her impact could take a different path. She developed a passion for using chemistry to solve health challenges. She now aspires to collaborate across disciplines to create innovative methods, tools, and medications that prevent or cure developmental diseases. Zanyah plans to achieve her goals by pursuing a Ph.D., expanding her network, and seizing opportunities like her current internship at the Massachusetts Institute of Technology. Beyond science, she enjoys reading, exercising, and practicing yoga. Her balance of chemistry, innovation, and personal wellness makes her flexible, adaptable, and open-minded—qualities valuable in any professional setting.

Abstract

A Class of Covalent Probes for Fluorescence-based Detection of Conformational Changes

Protein conformational change plays a crucial role in biological processes such as molecular recognition and signal transduction. Common techniques, including nuclear magnetic resonance (NMR) and circular dichroism (CD), are valuable but limited by their requirements for high sample concentrations, specialized instrumentation, and low throughput. To overcome these limitations, the Johnson Lab is developing a fluorescence-based method to monitor protein conformational changes. Specifically, we hypothesize that the reaction between 2,4,6-pyrylium salts and the amino group of lysine residues will enable us to track changes in fluorescence as this reaction progresses.
As a model protein system, I am applying this method to heat shock protein Hsp70, which undergoes substantial conformational change upon ATP hydrolysis, with fluorescence measured via a plate reader. We expect the spectral profile to reveal distinct differences between “open” (ATP-bound) and “closed” (ADP-bound) Hsp70. The application of our 2,4,6-pyrylium salt probes to two different Hsp70 homologs, Hsp72 and Hsc70, revealed an increase in fluorescence in both states, with the “open” conformation displaying higher fluorescence depending on the Hsp70 homolog, likely due to an increase in solvent-exposed lysines. Altogether, the success of these experiments represents an important step toward expanding pyrylium-salt-based protein chemistry to study protein conformational changes in biological processes, including the misfolding or aggregation of proteins involved in neurodegenerative diseases.