In Silico Mutagenesis and Docking Studies of Pseudomonas aeruginosa PA-IIL Lectin - Predicting Binding Modes and Energies
In Silico Mutagenesis and Docking Studies of Pseudomonas aeruginosa PA-IIL Lectin - Predicting Binding Modes and Energies
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DOI：
10.1021/ci8002107
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发表时间：
2008-11-01
影响因子：
5.6
通讯作者：
Koca, Jaroslav
中科院分区：
文献类型：
--
作者：
Adam, Jan;Kriz, Zdenek;Koca, Jaroslav
本文重点介绍了AutoDock和DOCK两种对接软件的应用。目的是研究钙依赖性细菌凝集素PA-IIL（来自铜绿假单胞菌）及其计算机模拟突变体与糖配体的相互作用。分配给钙离子的不同部分电荷的效果是测试和评估的最佳协议与晶体结构。利用分子动力学对DOCK的结果进行了进一步优化，并用AMBER软件进行了重新评分。对于这两种软件，根据预测准确性评估了对接结构和提供的结合能的一致性。这是通过将计算结果分别与晶体结构和实验测定的结合能进行比较来进行的。这两个对接软件的性能进行了评估，以及对所研究的问题。分子对接的方法被证明是有效的，在确定正确的结合模式的几何形状和部分也在预测突变引起的偏好变化。获得一个合理的预测凝集素-糖相互作用的计算机方法可能在未来。
This article is focused on the application of two types of docking software, AutoDock and DOCK. It is aimed at studying the interactions of a calcium-dependent bacterial lectin PA-IIL (from Pseudomonas aeruginosa) and its in silico mutants with saccharide ligands. The effect of different partial charges assigned to the calcium ions wits tested and evaluated in terms of the best agreement with the crystal structure. The results of DOCK were further optimized by molecular dynamics and rescored using AMBER. For both software, the agreement of the docked structures and the provided binding energies were evaluated in terms of prediction accuracy. This was carried Out by comparing the computed results to the crystal structures and experimentally determined binding energies, respectively. The performance of both docking software applied on a studied problem was evaluated as well. The molecular docking methods proved efficient in identifying the correct binding modes in terms of geometry and partially also in predicting the preference changes caused by mutation. Obtaining a reasonable in silico method for the prediction of lectin-saccharide interactions may be possible in the future.