Govindammal M, Kannan S, Srinivasan P, Prasath M
Department of Physics, Periyar University Centre for Post Graduate and Research Studies, Dharmapuri, 635 205, India.
Centre for High Computing, CSIR-Central Leather Research Institute (CLRI), Chennai, 600020, India.
Heliyon. 2022 May 26;8(5):e09539. doi: 10.1016/j.heliyon.2022.e09539. eCollection 2022 May.
Quercitrin is an anti-lung cancer agent. It is a naturally occurring flavonoid and its derivatives are mainly present in nuts and beverages. It is mainly available as a glycoside, and the quercitrin glycosides are found to prevent the metastasis of cancer. Quercitrin is optimized with 6-311++G(d,p) basis set using the B3LYP method to attain its minimum energy structure. The vibrational studies of the Quercitrin compound were elucidated with reference to Potential Energy Distribution (PED). The geometrical parameters were obtained and correlated with experimental values. To examine the nature of the charge transfer mechanism of Quercitrin, the HOMO-LUMO energy gap is computed. The anti-cancer activity of Quercitrin has been explored using molecular docking study that are used to estimate how the ligand interacts with protein, specifically to identify the best-fit orientation of the ligand, its binding mode, and intermolecular interactions of amino acid residues in the binding region of B-RAF kinase protein. The binding affinity of the compound Quercitrin (-7.14 kcal/mol) was found using AutoDock and validated with a Glide XP score in Schrodinger tool (-8.01 kcal/mol). MD simulations of protein-ligand complexes were monitored for 100 ns, from which the RMSD, RMSF, Rg, H-bonds, and interaction energy calculations were executed. From these investigations, it is identified that the compound quercitrin has maintained good structural stability, compactness, higher Hydrogen bonds, and interaction energies than the Imidazopyridinyl benzamide inhibitor.
槲皮苷是一种抗肺癌药物。它是一种天然存在的黄酮类化合物,其衍生物主要存在于坚果和饮料中。它主要以糖苷形式存在,并且发现槲皮苷糖苷可预防癌症转移。使用B3LYP方法在6-311++G(d,p)基组下对槲皮苷进行优化以获得其最低能量结构。参照势能分布(PED)对槲皮苷化合物进行振动研究。获得几何参数并与实验值进行关联。为了研究槲皮苷的电荷转移机制的性质,计算了HOMO-LUMO能隙。使用分子对接研究探索了槲皮苷的抗癌活性,该研究用于估计配体与蛋白质的相互作用方式,特别是确定配体的最佳拟合方向、其结合模式以及B-RAF激酶蛋白结合区域中氨基酸残基的分子间相互作用。使用AutoDock发现化合物槲皮苷的结合亲和力为-7.14 kcal/mol,并在Schrodinger工具中用Glide XP评分进行了验证(-8.01 kcal/mol)。对蛋白质-配体复合物进行了100 ns的分子动力学模拟,并据此进行了均方根偏差(RMSD)、均方根波动(RMSF)、回旋半径(Rg)、氢键和相互作用能计算。从这些研究中可以确定,与咪唑并吡啶基苯甲酰胺抑制剂相比,化合物槲皮苷具有良好的结构稳定性、紧凑性、更高的氢键和相互作用能。