Research Experiences for Undergraduates in Computational Methods with Applications in Materials Science
Major
Chemistry
College
College of Arts and Sciences
Research Mentor
Steven Gwaltney
Research Mentor's Department
Department of Chemistry
Research Center
Center for Computational Sciences
Abstract
Poster created as part of the Center for Computational Sciences' Research Experiences for Undergraduates in Computational Methods with Applications in Materials Science and presented at the 2024 Undergraduate Research Showcase.
Organophosphate (OP) poisoning disrupts nerve signaling by inhibiting acetylcholinesterase (AChE), an essential enzyme. Current oxime-based treatments for OP poisoning lack efficacy in severe cases due to blood-brain barrier (BBB) impermeability. A prior machine learning study identified promising AChE reactivators with BBB permeability and synthetic feasibility. Our study employed in silico docking simulations using AutoDock to evaluate the interactions between these potential reactivators and a sarin-inhibited human AChE model. The 35 compounds proposed in the earlier study, along with five known good AChE reactivators, were docked against a model of human AChE that was inhibited by the OP nerve agent sarin. While all the positive control molecules yielded good docking results, none of the newly proposed compounds did. The results of this docking analysis will inform the development of novel OP antidotes capable of reaching the brain and effectively reactivating AChE in sever poisoning scenarios. We suggest adding a docking screening to any future protocol designed to generate potential reactivators.
Presentation Date
Summer 8-2-2024
Keywords
organophosphate poisoning, enzyme docking
Recommended Citation
Pirger, Ryan and Gwaltney, Steven, "A docking Analysis of reactivators for sarin-inhibited acetylcholinestrase can aid in screening candidate compounds" (2024). Research Experiences for Undergraduates in Computational Methods with Applications in Materials Science. 6.
https://scholarsjunction.msstate.edu/ccs-reu/6