Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47906, USA.
J Cheminform. 2014 Apr 16;6:14. doi: 10.1186/1758-2946-6-14. eCollection 2014.
Protein-based pharmacophore models are enriched with the information of potential interactions between ligands and the protein target. We have shown in a previous study that protein-based pharmacophore models can be applied for ligand pose prediction and pose ranking. In this publication, we present a new pharmacophore-based docking program PharmDock that combines pose sampling and ranking based on optimized protein-based pharmacophore models with local optimization using an empirical scoring function.
Tests of PharmDock on ligand pose prediction, binding affinity estimation, compound ranking and virtual screening yielded comparable or better performance to existing and widely used docking programs. The docking program comes with an easy-to-use GUI within PyMOL. Two features have been incorporated in the program suite that allow for user-defined guidance of the docking process based on previous experimental data. Docking with those features demonstrated superior performance compared to unbiased docking.
A protein pharmacophore-based docking program, PharmDock, has been made available with a PyMOL plugin. PharmDock and the PyMOL plugin are freely available from http://people.pharmacy.purdue.edu/~mlill/software/pharmdock.
基于蛋白质的药效团模型富含配体与蛋白质靶标之间潜在相互作用的信息。我们在之前的研究中表明，基于蛋白质的药效团模型可用于配体构象预测和构象排序。在本出版物中，我们提出了一种新的基于药效团的对接程序 PharmDock，它将基于优化的基于蛋白质的药效团模型的构象采样和排序与使用经验评分函数的局部优化相结合。
在配体构象预测、结合亲和力估计、化合物排序和虚拟筛选方面对 PharmDock 的测试表明，其性能与现有和广泛使用的对接程序相当或更好。该对接程序在 PyMOL 中附带了一个易于使用的 GUI。该程序套件中包含了两个功能，允许根据以前的实验数据对对接过程进行用户定义的指导。与无偏对接相比，带有这些功能的对接表现出更好的性能。
提供了一个带有 PyMOL 插件的基于蛋白质药效团的对接程序 PharmDock。PharmDock 和 PyMOL 插件可从 http://people.pharmacy.purdue.edu/~mlill/software/pharmdock 免费获得。
