37th Annual Student Research Conference
Computational investigation of small-molecule inhibitors targeting He-PTP as a potential treatment for leukemia
Lauren E. Reid
Dr. Bill R. Miller, Faculty Mentor
Hematopoietic tyrosine phosphatase (He-PTP), a member of the kinase interaction motif (KIM) family of enzymes, is expressed exclusively in hematopoietic cells. Hematopoietic cells are characterized by their ability to differentiate into blood cells such as CD4+ T-cells (helper T-cells). Previous research has shown a negative correlation between overexpression of He-PTP and CD4+ T-cell activation. Furthermore, overexpression of He-PTP is associated with leukemia, making He-PTP a promising candidate for novel drug therapies. When expressed, He-PTP binds to and dephosphorylates mitogen-activated protein kinases (MAPKs). Once dephosphorylated, MAPKs are prevented from translocating to the nucleus and initiating transcription events that activate CD4+ T-cells and enhance the specific immune system response. This computational project utilized molecular docking and subsequent molecular dynamics simulations to determine binding efficiencies of prospective drugs to the active site of He-PTP. A thermodynamically favorable ligand capable of inhibiting the activity of He-PTP may elicit a stronger immune response to leukemia.
Keywords: He-PTP, Leukemia, Computational chemistry, Molecular docking, Molecular dynamics
Topic(s):Biochemistry and Molecular Biology
Chemistry
Biology
Presentation Type: Oral Presentation
Session: 107-2
Location: MG 1000
Time: 9:30