Apolipoprotein B mRNA Editing Enzyme 3B, or APOBEC3B (Figure 1), is a deaminase which converts cytosines to uracils in single-stranded DNA. Overexpression of APOBEC3B is thought to lead to epithelial cancers, such as breast and cervical. APOBEC3B is not currently or sufficiently treated with market medicines, and to further develop treatments for the listed cancers an inhibitor of APOBEC3B is being researched. About 7.8 million ligands collected from the ZINC12 docking database have been analyzed utilizing computational methods. Ligands are first docked using Auto Dock Qvina software, which provides a cutoff for which ligands are analyzed further. All ligands that pass the cutoff are simulated utilizing AMBER Molecular Dynamics (MD) for 250 ns to observe their behavior within the protein’s active site. Once MD is completed, all ligands are further analyzed utilizing free energy calculations, root mean squared deviation, and hydrogen bonding analysis. After completing MD analysis on the selected ligands, DOCK6 and the novel technique of <i>de novo</i> ligand growth are performed using the 25 best scoring ligands from the ZINC12 database to provide a scaffold from which to build more ligands. This provides several new ligands (for example, Figure 2) destined for MD analysis and provides several new candidates for effective competitive inhibitors of APOBEC3B.

Computational drug discovery of APOBEC3B inhibitors as a treatment for epithelial cancers

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