Department of Chemistry, School of Pharmaceutical Sciences, Guangzhou Medical University , Guangzhou , China .
J Enzyme Inhib Med Chem. 2014 Oct;29(5):702-9. doi: 10.3109/14756366.2013.845816. Epub 2013 Oct 24.
The molecular docking, MD simulation and binding free energy calculation were performed to explore the probable binding modes between PLA and tubulin. Through docking study, three possible binding sites for PLA were speculated as follows: the taxane site, the alternative site and a new site in α-tubulin. Then, 12.0 ns MD simulations show that these binding modes predicted by docking have been changed more or less, whereas the MD simulations offer more reliable binding details. The MM-PBSA binding free-energy calculations reasonably identify that the taxane site is the most favorable binding site of PLA and the alternative site is the secondary one, which can be used to explain some experimental facts. These studies theoretically resolve the priority of binding sites for PLA and offer the reliable binding modes between PLA and tubulin, and thus help to understanding the action mechanism for this kind of inhibitor.
采用分子对接、分子动力学模拟和结合自由能计算等方法，研究了 PLA 与微管蛋白可能的结合模式。通过对接研究，推测 PLA 可能有三个结合位点：紫杉烷结合位点、替代结合位点和α-微管蛋白中的新位点。然后，12.0ns 的 MD 模拟表明，对接预测的这些结合模式或多或少发生了变化，而 MD 模拟提供了更可靠的结合细节。MM-PBSA 结合自由能计算合理地确定了紫杉烷结合位点是 PLA 最有利的结合位点，替代结合位点是次要的结合位点，这可以用来解释一些实验事实。这些研究从理论上解决了 PLA 结合位点的优先级问题，并提供了 PLA 与微管蛋白之间可靠的结合模式，从而有助于理解这类抑制剂的作用机制。
