School of Pure and Applied Physics, Mahatma Gandhi University, Kottayam, Kerala 686560, India.
J Mol Model. 2011 Nov;17(11):2805-16. doi: 10.1007/s00894-011-0954-2. Epub 2011 Feb 2.
Curcumin is a natural phytochemical that exhibits a wide range of pharmacological properties, including antitumor and anticancer activities. The similarity in the shape of curcumin to DNA minor groove binding drugs is the motivation for exploring its binding affinity in the minor grooves of DNA sequences. Interactions of curcumin with DNA have not been extensively examined, while its pharmacological activities have been studied and documented in depth. Curcumin was docked with two DNA duplexes, d(GTATATAC)(2) and d(CGCGATATCGCG)(2), and molecular dynamics simulations of the complexes were performed in explicit solvent to determine the stability of the binding. In all systems, the curcumin is positioned in the minor groove in the A·T region, and was stably bound throughout the simulation, causing only minor modifications to the structural parameters of DNA. Water molecules were found to contribute to the stability of the binding of the ligand. Free energy analyses of the complexes were performed with MM-PBSA, and the binding affinities that were calculated are comparable to the values reported for other similar nucleic acid-ligand systems, indicating that curcumin is a suitable natural molecule for the development of minor groove binding drugs.
姜黄素是一种天然植物化学物质，具有广泛的药理活性，包括抗肿瘤和抗癌活性。姜黄素的形状与 DNA 小沟结合药物相似，这激发了人们探索其在 DNA 序列小沟中的结合亲和力。姜黄素与 DNA 的相互作用尚未得到广泛研究，但其药理活性已得到深入研究和记录。本文将姜黄素与两条 DNA 双链 d(GTATATAC)(2)和 d(CGCGATATCGCG)(2)对接，并在明胶溶剂中对复合物进行分子动力学模拟，以确定结合的稳定性。在所有系统中，姜黄素都位于 A·T 区域的小沟中，并在整个模拟过程中稳定结合，仅对 DNA 的结构参数产生微小的改变。发现水分子有助于配体的结合稳定。通过 MM-PBSA 对复合物进行了自由能分析，计算得到的结合亲和力与其他类似核酸-配体系统的报道值相当，表明姜黄素是开发小沟结合药物的合适天然分子。
