Insights into the Molecular Mechanisms of Protein-Ligand Interactions by Molecular Docking and Molecular Dynamics Simulation: A Case of Oligopeptide Binding Protein
Insights into the Molecular Mechanisms of Protein-Ligand Interactions by Molecular Docking and Molecular Dynamics Simulation: A Case of Oligopeptide Binding Protein
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DOI：
10.1155/2018/3502514
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Chen, Zhiguo
中科院分区：
文献类型：
--
作者：
Fu, Yi;Zhao, Ji;Chen, Zhiguo
蛋白质-配体相互作用是信号转导、免疫反应和基因调控的必要前提。蛋白质-配体相互作用的研究对于理解生物学调控机制具有重要意义，并且它们为设计和发现新的药物靶点提供了理论基础。本研究利用AutoDock 4.2软件对蛋白质与配体的相互作用进行了分析。在AutoDock 4.2软件中，采用了一种新的搜索算法--随机漂移粒子群优化与局部搜索的混合算法（LRDPSO）和经典的拉马克遗传算法（LGA）作为能量优化算法。对每个对接算法的最佳构象进行分子动力学（MD）模拟，以进一步分析蛋白质-配体相互作用的分子机制。在这里，我们分析了蛋白质受体和配体之间的结合能，对接区域的盐桥和氢键的相互作用，以及复杂的解折叠过程中的结构变化。我们对这些复合物的比较突出了两种对接方法之间蛋白质-配体相互作用的差异。研究还表明，盐桥和氢键相互作用在蛋白质-配体稳定性中起着至关重要的作用。目前的工作重点是提取对接相互作用的确定性特征，从他们的动态特性，这是很重要的了解生物功能，并确定哪些氨基酸残基是至关重要的对接相互作用。
Protein-ligand interactions are a necessary prerequisite for signal transduction, immunoreaction, and gene regulation. Protein-ligand interaction studies are important for understanding the mechanisms of biological regulation, and they provide a theoretical basis for the design and discovery of new drug targets. In this study, we analyzed the molecular interactions of protein-ligand which was docked by AutoDock 4.2 software. In AutoDock 4.2 software, we used a new search algorithm, hybrid algorithm of random drift particle swarm optimization and local search (LRDPSO), and the classical Lamarckian genetic algorithm (LGA) as energy optimization algorithms. The best conformations of each docking algorithm were subjected to molecular dynamic (MD) simulations to further analyze the molecular mechanisms of protein-ligand interactions. Here, we analyze the binding energy between protein receptors and ligands, the interactions of salt bridges and hydrogen bonds in the docking region, and the structural changes during complex unfolding. Our comparison of these complexes highlights differences in the protein-ligand interactions between the two docking methods. It also shows that salt bridge and hydrogen bond interactions play a crucial role in protein-ligand stability. The present work focuses on extracting the deterministic characteristics of docking interactions from their dynamic properties, which is important for understanding biological functions and determining which amino acid residues are crucial to docking interactions.