Goto Junichi, Kataoka Ryoichi, Muta Hajime, Hirayama Noriaki
Computational Science Department, Science & Technology Systems Division, Ryoka Systems, Inc., 1-28-38 Shinkawa, Chuo-ku, Tokyo 104-0033, Japan.
J Chem Inf Model. 2008 Mar;48(3):583-90. doi: 10.1021/ci700352q. Epub 2008 Feb 16.
ASEDock is a novel docking program based on a shape similarity assessment between a concave portion (i.e., concavity) on a protein and the ligand. We have introduced two novel concepts into ASEDock. One is an ASE model, which is defined by the combination of alpha spheres generated at a concavity in a protein and the excluded volumes around the concavity. The other is an ASE score, which evaluates the shape similarity between the ligand and the ASE model. The ASE score selects and refines the initial pose by maximizing the overlap between the alpha spheres and the ligand, and minimizing the overlap between the excluded volume and the ligand. Because the ASE score makes good use of the Gaussian-type function for evaluating and optimizing the overlap between the ligand and the site model, it can pose a ligand onto the docking site relatively faster and more effectively than using potential energy functions. The posing stage through the use of the ASE score is followed by full atomistic energy minimization. Because the posing algorithm of ASEDock is free from any bias except for shape, it is a very robust docking method. A validation study using 59 high-quality X-ray structures of the complexes between drug-like molecules and the target proteins has demonstrated that ASEDock can faithfully reproduce experimentally determined docking modes of various druglike molecules in their target proteins. Almost 80% of the structures were reconstructed within the estimated experimental error. The success rate of approximately 98% was attained based on the docking criterion of the root-mean-square deviation (RMSD) of non-hydrogen atoms (< or = 2.0 A). The markedly high success of ASEDock in redocking experiments clearly indicates that the most important factor governing the docking process is shape complementarity.
ASEDock是一种基于蛋白质上凹面（即凹陷）与配体之间形状相似性评估的新型对接程序。我们在ASEDock中引入了两个新概念。一个是ASE模型，它由蛋白质凹陷处生成的α球与凹陷周围的排除体积的组合定义。另一个是ASE分数，它评估配体与ASE模型之间的形状相似性。ASE分数通过最大化α球与配体之间的重叠，并最小化排除体积与配体之间的重叠来选择和优化初始姿态。由于ASE分数很好地利用了高斯型函数来评估和优化配体与位点模型之间的重叠，因此与使用势能函数相比，它可以更快、更有效地将配体放置到对接位点上。通过使用ASE分数的姿态阶段之后是全原子能量最小化。由于ASEDock的姿态算法除了形状之外没有任何偏差，所以它是一种非常稳健的对接方法。使用59个类药物分子与靶蛋白复合物的高质量X射线结构进行的验证研究表明，ASEDock可以忠实地重现各种类药物分子在其靶蛋白中实验确定的对接模式。几乎80%的结构在估计的实验误差范围内重建。基于非氢原子的均方根偏差（RMSD）（<或=2.0 Å）的对接标准，成功率达到了约98%。ASEDock在重新对接实验中的显著高成功率清楚地表明，控制对接过程的最重要因素是形状互补性。
