在过去的三十年里,随着生活方式的实质性改变,体重增加的趋势增加了,这导致了影响个人福祉的重大后果。脂肪量和肥胖相关(FTO)基因参与食物摄入和能量消耗,并通过阻碍大脑产生的信号在调节稳态和控制能量消耗中起关键作用。食用海藻由于其健康益处而被证明可以增强饱腹感。
对植物来源的抗肥胖化合物和海藻化合物进行了广泛筛选,并验证了ADME特性和毒性预测。Further,将排名靠前的化合物与FTO蛋白对接,以鉴定潜在的抑制剂,并进行分子动力学模拟研究,以了解配体蛋白复合物的结合稳定性.最后,进行MM/PBSA研究以计算蛋白质-配体复合物的结合自由能。
通过对1,210种化合物的虚拟筛选,443个化合物显示出小于-7.00kcal/mol的良好对接分数。443种化合物的药物相似性筛选显示只有369种化合物符合这些性质。进一步的毒性预测产生了30种无毒化合物。分子对接研究揭示了四种排名最高的海洋化合物。最后,来自海洋红藻Laurenciasp的RL074(2-羟基脲酮B)和RL442(10-乙酰氧基安醇)在分子动力学模拟研究中显示出良好的稳定性。MM/PBSA结果显示BT012(24ε-氢过氧-6β-羟基-24-乙基胆甾烯-4,-28(29)-二烯-3-酮),一种来自褐藻的含氧岩藻甾醇,具有较高的结合能。因此,根据获得的所有数据,可以得出结论,三种海藻化合物,BT012、RL074和RL442可作为靶向FTO的潜在抗肥胖先导化合物。
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.
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.
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.