Design of potential IKK-βinhibitors using molecular docking and molecular dynamics techniques for their anti-cancer potential.
Design of potential IKK-βinhibitors using molecular docking and molecular dynamics techniques for their anti-cancer potential.
复制标题
使用分子对接和分子动力学技术设计潜在的 IKK-β 抑制剂，以发挥其抗癌潜力。
DOI：
10.2174/1573409916666200102121505
复制
发表时间：
2020
影响因子：
1.7
通讯作者：
C. B. Singh
中科院分区：
文献类型：
--
作者：
S. P. Singh;I. Hussain;B. K. Konwar;R. Deka;C. B. Singh
目的和目标
评价一组70种植物化学物质结合核因子κ B激酶β（IKK-β）抑制剂的潜在能力，IKK-β是癌症和炎症性疾病的主要靶点。
材料和方法
利用DFT分子对接技术对70种植物化学物质进行IKK-β酶活性筛选，并将筛选出的最佳对接结果进行分子动力学模拟。还对最高对接命中进行了adme毒性分析。
结果
芝麻素、matairesinol和白藜芦醇是最高的对接命中，总得分分别为-413kJ/mol、-398.11kJ/mol和266.73kJ/mol。Glu 100和Gly 102是最常见的相互作用残基。分子动力学模拟结果表明，三种化合物的结合自由能分别为-107.62 kJ/mol、-120.37 kJ/mol和-40.56 kJ/mol。DFT计算表明了化合物的稳定性。ADME-毒性预测观察到这些化合物在煮鸡蛋的允许范围内，并且不违反药理学标准、药物相似性等任何规则。结论：本研究解释了膳食植物化学物质是IKK-β酶的有效抑制剂，具有良好的结合亲和力和较小的毒性作用。事实上，植物衍生分子的使用逐渐增加，因为与化疗相比，其副作用较小。该研究还提供了植物化学物质抑制IKK-β酶的见解。这项研究也将有助于了解某些膳食植物化学物质在治疗癌症中的抑制模式。
AIM AND OBJECTIVE
To evaluate a set of seventy phytochemicals for their potential ability to bind the inhibitor of nuclear factor kappaB kinase beta (IKK-β) which is a prime target for cancer and inflammatory diseases.
MATERIALS AND METHODS
Seventy phytochemicals were screened against IKK-β enzyme using DFT-based molecular docking technique and the top docking hits were carried forward for molecular dynamics (MD) simulation protocols. The adme-toxicity analysis was also carried out for the top docking hits.
RESULTS
Sesamin, matairesinol and resveratrol were found to be the top docking hits with a total score of -413 kJ/mol, -398.11 kJ/mol and 266.73 kJ/mol respectively. Glu100 and Gly102 were found to be the most common interacting residues. The result from MD simulation observed a stable trajectory with a binding free energy of -107.62 kJ/mol for matairesinol, -120.37 kJ/mol for sesamin and -40.56 kJ/mol for resveratrol. The DFT calculation revealed the stability of the compounds. The ADME-Toxicity prediction observed that these compounds fall within the permissible area of Boiled-Egg and it does not violate any rule for pharmacological criteria, drug-likeness etc. Conclusion: The study interprets that dietary phytochemicals are potent inhibitors of IKK-β enzyme with favourable binding affinity and less toxic effects. In fact, there is a gradual rise in the use of plant-derived molecules because of its lesser side effects compared to chemotherapy. The study has also provided an insight by which the phytochemicals inhibited the IKK-β enzyme. The investigation would also provide in understanding the inhibitory mode of certain dietary phytochemicals in treating cancer.