Developing novel inhibitors for Striatal Enriched Tyrosine Phosphatase (STEP) using computational methods

Dagmawit Kebede
Dr. Andrew Kauffmann and Dr. Bill Miller III (A.T. Still University), Faculty Mentors

Striatal Enriched Tyrosine Phosphatase (STEP) is a brain-specific enzyme that regulates synaptic functioning by dephosphorylating key signaling proteins. Elevated STEP activity disrupts synaptic function and is implicated in neurodegenerative and psychiatric disorders, making it a promising drug target. This study employed molecular docking using AutoDock Vina to screen 2.5 million ligands from the ZINC database for potential STEP inhibitors. Top-scoring ligands underwent molecular dynamics (MD) simulations using Amber to assess stability and binding interactions in physiological conditions. Docking results identified promising ligands, with the highest binding affinity of -8.7 kcal/mol. Free energy calculations further supported their potential as STEP inhibitors, slightly outperforming a control drug. While these findings highlight promising leads, experimental validation and optimization are necessary to confirm therapeutic efficacy. Future studies will refine these compounds and evaluate their potential for inhibiting STEP.

Keywords: STEP, molecular docking, molecular dynamics, synaptic function, neurodegeneration, drug discovery

Topic(s):Chemistry
Biochemistry and Molecular Biology
Biology

Presentation Type: Oral Presentation

Session: TBA
Location: TBA
Time: TBA