Flexible docking in solution using metadynamics
Flexible docking in solution using metadynamics
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DOI：
10.1021/ja0445950
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发表时间：
2005-03-02
影响因子：
15
通讯作者：
Parrinello, M
中科院分区：
文献类型：
--
作者：
Gervasio, FL;Laio, A;Parrinello, M
我们将最近发展的元动力学方法应用于水溶液中柔性受体的配体对接。这种方法模拟了配体退出或进入酶的真实动力学，从而重建了自由能表面。我们将其应用于四种对接案例：β -胰蛋白酶/苄脒、β -胰蛋白酶/氯苯脒、免疫球蛋白McPC-603/磷胆碱和周期蛋白依赖性激酶2/星孢素。在研究的每一种情况下，该方法都能预测到对接的几何形状和对接的自由能。与许多其他可用的方法相比，它的附加价值在于它重建了完整的自由能面，包括所有相关的最小值和它们之间的势垒。
We apply our recently developed metadynamics method to the docking of ligands on flexible receptors in water solution. This method mimics the real dynamics of a ligand exiting or entering an enzyme and in so doing reconstructs the free energy surface. We apply it to four docking cases: beta-trypsin/benzamidine, beta-trypsin/chlorobenzamidine, immunoglobulin McPC-603/phosphocholine, and cyclin-dependent kinase 2/staurosporine. In every case studied, the method is able to predict the docked geometry and the free energy of docking. Its added value with respect to many other available methods is that it reconstructs the complete free energy surface, including all the relevant minima and the barriers between them.