Docking flexible peptide to flexible protein by molecular dynamics using two implicit-solvent models: an evaluation in protein kinase and phosphatase systems.
Docking flexible peptide to flexible protein by molecular dynamics using two implicit-solvent models: an evaluation in protein kinase and phosphatase systems.
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DOI：
10.1021/jp907375b
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发表时间：
2009-10-29
期刊：
影响因子：
--
通讯作者：
Wong CF
中科院分区：
文献类型：
--
作者：
Huang Z;Wong CF
蛋白质-配体对接位姿的可靠预测需要适当考虑诱导配合效应。将配体和蛋白质作为柔性分子处理仍然具有挑战性，因为涉及到许多自由度。多肽是一种特别难以研究的配体，因为它们具有极强的灵活性。在这项研究中，我们使用两种隐式溶剂模型测试了基于分子动力学的模拟退火循环方案，该方案将肽对接到四种蛋白激酶和两种磷酸酶：距离依赖的介电模型（ε(r)=4r）和称为GBMV的广义Born模型。我们发现简单的ε(r)=4r模型比昂贵的GBMV模型更能识别对接位姿。此外，将一种隐式溶剂模型得到的结构与另一种隐式溶剂模型进行对比，确定了所有六种体系的良好对接姿态。在评分中加入蛋白质能量也能改善结果。
Reliable prediction of protein-ligand docking pose requires proper account of induced fit effects. Treating both the ligand and the protein as flexible molecules is still challenging because many degrees of freedom are involved. Peptides are one type of ligands that are particularly difficult to study because of their extreme flexibility. In this study, we tested a molecular dynamics-based simulated-annealing cycling protocol in docking peptides to four protein kinases and two phosphatases using two implicit-solvent models: a distance-dependent dielectric model (ε(r)=4r) and a version of the Generalized Born model termed GBMV. We found that the simpler ε(r)=4r model identified docking pose better than the more expensive GBMV model. In addition, rescoring structures obtained from one implicit-solvent model with the other identified good docking poses for all six systems studied. Including protein energy in scoring also improved results.
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