Apolipoprotein B mRNA Editing Enzyme 3B, or APOBEC3B, is a deaminase that converts cytosines to uracils in single-stranded DNA. Overexpression of APOBEC3B has been linked to numerous epithelial cancers, including breast and cervical cancer. Epithelial cancers account for nearly ninety percent of all cancers. The current study aims to discover a novel inhibitor of APOBEC3B as a potential treatment for the listed cancers and Hepatitis B.<br/>Approximately 6 million molecules retrieved from the ZINC12 docking database are analyzed utilizing various computational methods. Initially, these molecules are docked using the qvina software, which indicates the potential of these molecules as APOBEC3B inhibitors. The top ten percent of these molecules are further analyzed using AMBER Molecular Dynamics (MD) for 250 nanoseconds in order to observe their behavior within the protein's active site. After MD, all molecules are further analyzed utilizing free energy calculations, root mean square deviation, and hydrogen bonding.<br/>Preliminary data shows several promising potential inhibitors of APOBEC3B. Overall, around 60 molecules have been simulated and analyzed. These 60 molecules have had their root mean square deviation calculated and graphed. From this graph, we can see where the protein is most stable. We compare this data to the stability of the protein by itself. Each simulation has also been further analyzed using free energy calculations. These calculations give us a generalized score that indicates how well our inhibitors are binding to APOBEC3B as a function of time. These scores from the 60 molecules are then compared to each other to determine which of them are stabilizing the protein best.<br/>Several of the 60 inhibitors have been found to be very promising. Further inhibitors will be analyzed and be put through the same processes. The best of these inhibitors will be modified and analyzed to find the best competitive inhibitor of APOBEC3B.

Computational drug design for inhibition of cancer promoting APOBEC3B

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.