Hobani Yahya, Jerah Ahmed, Bidwai Anil
College of Applied Medical Sciences Jazan University, Jazan, Kingdom of Saudi Arabia.
Index Medical College Hospital & Research Centre, Indore, Madhya Pradesh, India.
Bioinformation. 2017 Mar 31;13(3):63-66. doi: 10.6026/97320630013063. eCollection 2017.
Interaction of curcumin (CUR) with the enzyme dihydrofolate reductase (DHFR) was studied by molecular docking using AutoDock 4.2 as the docking software application. AutoDock 4.2 software serves as a valid and acceptable docking application to study the interactions of small compounds with proteins. Interactions of curcumin with DHFR were compared to those of methotrexate (MTX), a known inhibitor of the enzyme. The calculated free energy of binding (ΔG binding) shows that curcumin (ΔG = -9.02 kcal/mol; Ki = 243 nM) binds with affinity comparable to or better than MTX (ΔG = -8.78 kcal/mol; Ki = 363 nM). Binding interactions of curcumin with active site residues of the enzyme are also predicted. Curcumin appears to bind in a bent conformation making extensive VDW contacts in the active site of the enzyme. Hydrogen bonding and pi-pi interaction with key active site residues are also observed. Thus, curcumin can be considered as a good lead compound in the development of new inhibitors of DHFR, which is a potential target of anti-cancer drugs. The results of these studies can serve as a starting point for further computational and experimental studies.
使用AutoDock 4.2作为对接软件应用程序，通过分子对接研究了姜黄素（CUR）与二氢叶酸还原酶（DHFR）的相互作用。AutoDock 4.2软件是研究小分子化合物与蛋白质相互作用的有效且可接受的对接应用程序。将姜黄素与DHFR的相互作用与甲氨蝶呤（MTX）（该酶的已知抑制剂）的相互作用进行了比较。计算得到的结合自由能（ΔG结合）表明，姜黄素（ΔG = -9.02 kcal/mol；Ki = 243 nM）的结合亲和力与MTX相当或更好（ΔG = -8.78 kcal/mol；Ki = 363 nM）。还预测了姜黄素与该酶活性位点残基的结合相互作用。姜黄素似乎以弯曲构象结合，在酶的活性位点形成广泛的范德华接触。还观察到与关键活性位点残基的氢键和π-π相互作用。因此，姜黄素可被视为开发DHFR新抑制剂的良好先导化合物，DHFR是抗癌药物的潜在靶点。这些研究结果可作为进一步计算和实验研究的起点。
