Computational study of potential inhibitors for fat mass and obesity-associated protein from seaweed and plant compounds

BACKGROUND: Over the past three decades, with substantial changes in lifestyle, the tendency to gain weight has increased, which is resulting in significant consequences affecting an individual’s well-being. The fat mass and obesity-associated (FTO) gene is involved in food intake and energy expenditure and plays a crucial role in regulating homeostasis and controlling energy expenditure by hindering signals that generate from the brain. Edible seaweeds have been shown to enhance satiety owing to their health benefits. METHODS: Extensive screening of plant-derived anti-obesity compounds and seaweed compounds was conducted and validated for ADME properties and toxicity prediction. Further, the top ranked compounds were docked against the FTO protein to identify potential inhibitors and were subjected to molecular dynamic simulation studies to understand the binding stability of ligand protein complex. Finally, MM/PBSA studies were performed to calculate the binding free energy of the protein-ligand complexes. RESULTS: Through the virtual screening of 1,210 compounds, 443 compounds showed good docking scores less than −7.00 kcal/mol. Drug likeness screenings of 443 compounds showed that only 369 compounds were in accordance with these properties. Further toxicity prediction resulted in 30 non-toxic compounds. Molecular docking studies revealed four top ranked marine compounds. Finally, RL074 (2-hydroxyluzofuranone B) and RL442 (10-acetoxyangasiol) from marine red alga Laurencia sp showed good stability from molecular dynamic simulation studies. MM/PBSA results revealed that BT012 (24ε-hydroperoxy-6β-hydroxy-24-ethylcholesta-4,-28(29)-dien-3-one), an oxygenated fucosterol from brown alga Turbinaria conoides, possessed higher binding energy. Hence, with all the data obtained it could be concluded that three seaweed compounds, BT012, RL074 and RL442, may act as a potential anti-obesity lead compound in targeting FTO.