ColDock: Concentrated Ligand Docking with All-Atom Molecular Dynamics Simulation,The Journal of Physical Chemistry B

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ColDock: Concentrated Ligand Docking with All-Atom Molecular Dynamics Simulation
The Journal of Physical Chemistry B ( IF 2.8 ) Pub Date : 2018-07-11 , DOI: 10.1021/acs.jpcb.8b02756
Kazuhiro Takemura , Chika Sato , Akio Kitao ₁

Affiliation

We propose a simple but efficient and accurate method to generate protein–ligand complex structures, called Concentrated ligand Docking (ColDock). This method consists of multiple independent molecular dynamics simulations in which ligands are initially distributed randomly around a protein at relatively high concentration (∼100 mM). This condition significantly increases the probability of the ligand exploring the protein surface, which induces spontaneous ligand binding to the correct binding sites within a 100 ns MD. After clustering of the protein-bound ligand poses, representatives of the populationally dominant clusters are considered as predicted ligand poses. We applied ColDock to four cases starting from holo protein structures and showed that ColDock can generate “correct” ligand poses very similar to the crystal complex structures. Correct ligand poses are also well reproduced in three out of four cases started from apo structures, with the exception being a case with an initially closed binding pocket. The results indicate that ColDock can be used as a protein–ligand docking as long as the ligand binding pocket is initially open. Plausible protein–ligand complex structures can be easily generated by conducting the ColDock procedure using standard MD simulation software.

中文翻译：

ColDock：具有全原子分子动力学模拟的浓配体对接

我们提出了一种简单但有效且准确的方法来生成蛋白质-配体复杂的结构，称为浓缩配体对接（ColDock）。该方法由多个独立的分子动力学模拟组成，其中配体最初以相对较高的浓度（约100 mM）随机分布在蛋白质周围。这种情况显着增加了配体探索蛋白质表面的可能性，从而诱导了自发的配体与100 ns MD内正确的结合位点结合。蛋白质结合的配体姿势聚类后，群体优势簇的代表被视为预测的配体姿势。我们将ColDock应用于从完整蛋白质结构开始的4种情况下，结果表明ColDock可以产生与晶体复合物结构非常相似的“正确”配体姿势。从apo结构开始，在四分之三的情况下，正确的配体姿势也能很好地再现，例外的情况是最初带有封闭的结合袋。结果表明，只要配体结合口袋最初是开放的，ColDock就可以用作蛋白质-配体对接。通过使用标准的MD模拟软件进行ColDock程序，可以容易地生成合理的蛋白质-配体复杂结构。

更新日期：2018-07-12

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