36th Annual Student Research Conference
Early Discovery and Comparison of Striatum-enriched (STEP) and Hematopoietic (He-PTP) Protein Tyrosine Phosphatase Inhibitors Utilizing Computational Methods
Mackenzie E. Sweeney
Dr. Bill R. Miller, Faculty Mentor
Striatum-enriched (STEP) and hematopoietic (He-PTP) protein tyrosine phosphatases belonging to the kinase interaction motif (KIM) phosphatase family could be targeted by small-molecule inhibitors to advance therapeutic treatment of neurologic and hematologic disorders. STEP is thought to mediate neuroplasticity in the brain, and its overexpression is associated with Alzheimer’s, schizophrenia, and fragile-X syndrome. He-PTP is thought to influence immune response of hematopoietic (blood-producing) cells, and its overexpression is associated with leukemias. Current STEP inhibitors do not exhibit STEP specificity and are difficult to synthesize; inhibitors of He-PTP have not been identified. Computational methods can streamline the discovery of inhibitors by determining ligand binding efficiency and selectivity within the KIM phosphatase family. This project utilized molecular docking and molecular dynamics to compare inhibitory properties of current FDA-approved drugs using the WPD protein loop specific to KIM phosphatases as a binding site for both STEP and He-PTP.
Keywords: protein tyrosine phosphatase, hematopoietic PTP, striatum-enriched PTP, molecular docking, molecular dynamics, small-molecule inhibitors
Topic(s):Chemistry
Biochemistry and Molecular Biology
Presentation Type: Oral Presentation
Session: 107-4
Location: MG 2001
Time: 9:15