Graduation Year


Document Type




Degree Name

Master of Science (M.S.)

Degree Granting Department


Major Professor

Wayne C. Guida, Ph.D.

Co-Major Professor

Henry L. Woodcock, Ph.D.

Committee Member

James W. Leahy, Ph.D.

Committee Member

Yu Chen, Ph.D.


Clonixeril, Clonixin, Consensus Docking, DMXAA, Site-Restricted


The work contained in this thesis introduces a protein known as STING, an acronym for STimulator of INnterferon Genes, an immunosurveillance ER-membrane bound adapter protein critical to regulating the innate immune response in humans. The first chapter provides an overview of the STING pathway, outlines STING’s potential as a therapeutic target of interest, and delineates the primary challenges researchers encounter when designing small molecules to modulate the activity of STING. Current efforts in developing STING modulators have focused on devising agonists to up-regulate the STING pathway as a possible therapeutic for human cancers based on the chemical scaffold of STING’s native ligand, 2’,3’-cGAMP, a cyclic dinucleotide (CDN).

However, previous research has presented modest benefits and limited practical use for their efforts. As a result, the second chapter presents a simple computational modeling protocol termed site-restricted docking that can be incorporated into existing computational workflows to screen vast libraries of monomeric chemical compounds in identifying potential STING activators or inhibitors.

Furthermore, the third and final chapter outlines the modeling campaign devised to screen potential STING modulators and illustrates the importance protein conformation has on STING modulation.