Title

The Proposal of a Dopamine Reuptake Inhibiting Toxin

School Name

South Carolina Governor's School for Science and Mathematics

Grade Level

12th Grade

Presentation Topic

Biochemistry

Presentation Type

Mentored

Abstract

This research explored the design of a toxin that could bind well to a dopamine reuptake inhibitor to stimulate addiction. This acts as proof of concept that small changes to a toxin’s structure can lead to additional biological activity. This was primarily performed through the use of Avogadro and PyRx, with the former being used to create molecules and the latter simulating binding strength to a dopamine transport macromolecule. Multiple molecules were created for testing, each based on anatoxin-a, a toxic substance, and desipramine, a dopamine reuptake inhibitor. Variations included being bound together by a shared nitrogen, attaching despiramine’s carbon rings to anatoxin-a’s, and adding a ketone with a carbon and an oxygen as a means of attachment. After all five docking calculations were done, the fused molecule where anatoxin-a and desipramine were bound by a shared nitrogen bound the best, revealing a binding energy of -9.6 kcal/mol in PyRx. Other results were close, off by a few tenths of a kcal/mol, overall the fused molecule worked the most for what was needed. It is unclear how feasible this molecule would be in a practical setting. It is unknown if it could be synthesized, it is also unknown if the added desipramine could offset anatoxin-a’s deadliness enough to allow room for addiction, or potentially offsetting the toxic effects completely to create a new therapeutical molecule. Experimental testing would be needed to assess the activity of the newly created molecule and determine its toxicity, addiction potential, or therapeutic potential.

Location

HSS 202

Start Date

4-2-2022 11:00 AM

Presentation Format

Oral Only

Group Project

No

COinS
 
Apr 2nd, 11:00 AM

The Proposal of a Dopamine Reuptake Inhibiting Toxin

HSS 202

This research explored the design of a toxin that could bind well to a dopamine reuptake inhibitor to stimulate addiction. This acts as proof of concept that small changes to a toxin’s structure can lead to additional biological activity. This was primarily performed through the use of Avogadro and PyRx, with the former being used to create molecules and the latter simulating binding strength to a dopamine transport macromolecule. Multiple molecules were created for testing, each based on anatoxin-a, a toxic substance, and desipramine, a dopamine reuptake inhibitor. Variations included being bound together by a shared nitrogen, attaching despiramine’s carbon rings to anatoxin-a’s, and adding a ketone with a carbon and an oxygen as a means of attachment. After all five docking calculations were done, the fused molecule where anatoxin-a and desipramine were bound by a shared nitrogen bound the best, revealing a binding energy of -9.6 kcal/mol in PyRx. Other results were close, off by a few tenths of a kcal/mol, overall the fused molecule worked the most for what was needed. It is unclear how feasible this molecule would be in a practical setting. It is unknown if it could be synthesized, it is also unknown if the added desipramine could offset anatoxin-a’s deadliness enough to allow room for addiction, or potentially offsetting the toxic effects completely to create a new therapeutical molecule. Experimental testing would be needed to assess the activity of the newly created molecule and determine its toxicity, addiction potential, or therapeutic potential.