Molecular docking based on in silico screening of nci diversity sets for potent inhibitors of apobec3a enzyme

APOBEC3A (A3A) deaminates cytosine into uracil in single-stranded DNA (ssDNA). Failure to repair this genomic aberration resulting C-to-T or C-to-G mutations and further undesirable outcomes in the development of tumor, metastasis, and drug resistance. Therefore, a small molecule capable to disrupt the catalytic function of A3A has been predicted to offer potential therapeutic benefits. In this present study, we performed an in-silico screening against 2000 structurally diverse small molecules from the National Cancer Institute (NCI) database with reported anti-cancer properties. We used two different docking programs, AutoDock/Vina and GOLD, followed by interaction analysis between protein and ligands. Three potential compounds were identified with high scoring functions that bind to A3A-competitive site domain, mainly with the centralized zinc cofactor and amino acid residues through hydrogen bond and alkyl hydrophobic interaction. The findings from this work could lay the groundwork for future drug design and validation studies against A3A enzyme.