39th Annual Student Research Conference
Computational discovery of a small molecule inhibitor of APOBEC3B as a potential treatment for a variety of cancers
Alexandra M. Kliethermes
Dr. Bill R. Miller (A.T. Still University) and Dr. Stephanie Maiden, Faculty Mentors
Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3B (APOBEC3B) is a non-essential DNA cytosine deaminase that catalyzes the conversion of cytosine to uracil in single-stranded DNA (ssDNA). The APOBEC family of proteins contributes to immune defense by targeting parasites and viral genomes. APOBEC3B, a mammal-specific enzyme, promotes tumorigenesis and cancer progression when overexpressed; computational studies can identify small molecules/ ligands that can act as a competitive inhibitor and potential cancer treatment. This study aims to achieve this by designing de novo ligands using DOCK6 and evaluating their binding interactions with APOBEC3B. Zinc parameterization using GAMESS-US was performed to develop force-field parameters for the zinc active site of the APOBEC3B protein. These force fields are applied in molecular dynamics (MD) simulations to model ligand-induced structural changes in APOBEC3B and to calculate binding free energies.
Keywords: APOBEC3B, Computational Chemistry, Cancer
Topic(s):Biochemistry and Molecular Biology
Chemistry
Biology
Presentation Type: Oral Presentation
Session: -3
Location: MG 1000
Time: 1:30