Extra virgin olive oil is the principal source of dietary fat in the Mediterranean diet and is considered to have beneficial health effects. There is evidence to suggest that the phenolic compounds within Olea europaea have the ability to inhibit lysine-specific demethylase 1 (LSD1). This is an epigenetic enzyme that removes methyl groups from histone proteins and regulates gene transcription. Conversely, SET domain-containing protein 7 (SETD7) has opposing enzymatic activity and is a histone methyltransferase. Due to the involvement of these proteins in a number of pathological processes, including cancer and diabetes, further research needs to be conducted into the way in which they can be targeted. A large number of phenolic compounds (>200) have been identified in Olea europaea. To help expedite the discovery of promising lead compounds, in this study, in silico molecular docking methods were used to investigate the molecular binding properties of the phenolic compounds obtained from the OliveNet™ database to LSD1 and its variants, LSD2, and SETD7. Numerous Olea europaea phenolic compounds were predicted to bind to the epigenetic enzymes and several had stronger binding affinities than the LSD1 and SETD7 positive control inhibitors. The protein-ligand interactions of the phenolic compounds were also compared to known inhibitors and the molecular docking results suggest that the flavonoids, secoiridoids and glucosides may bind particularly strongly to the epigenetic regulators. Overall, several ligands were identified as lead compounds from this research and their potential inhibitory activity could be validated further in the laboratory.
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