LEADS-PEP: A Benchmark Data Set for Assessment of Peptide Docking Performance
LEADS-PEP: A Benchmark Data Set for Assessment of Peptide Docking Performance
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DOI：
10.1021/acs.jcim.5b00234
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发表时间：
2016-01-01
影响因子：
5.6
通讯作者：
Windshuegel, Bjoern
中科院分区：
文献类型：
--
作者：
Hauser, Alexander Sebastian;Windshuegel, Bjoern
随着人们对多肽治疗的兴趣日益浓厚，多肽对接等计算方法的应用也越来越受到重视。为了评估肽定位对接方案的适用性，支持肽特异性对接工具的开发，迫切需要一个独立构建的基准数据集。在这里，我们提出了用于评估肽对接性能的LEADS-PEP基准数据集。使用合理和公正的工作流程，53蛋白肽复合物的肽长度范围从3到12个残基选择。该数据集可在www.leads-x.org上公开访问。在第二步，我们评估了几个小分子对接程序的潜力，以重现肽构象存在于铅- pep中。虽然大多数被测试的程序都能够产生小肽的天然结合模式，但只有Surflex-Dock和AutoDock Vina对含有超过五个残基的肽表现得相当好。利用评分函数ChemPLP、ChemScore和ASP对对接姿势进行评分，进一步增加了排名靠前的近原生构象的数量。我们的研究结果表明，小分子对接程序是专门的肽对接程序的一个良好和快速的替代方案。
With increasing interest in peptide-based therapeutics also the application of computational approaches such as peptide docking has gained more and more attention. In order to assess the suitability of docking programs for peptide placement and to support the development of peptide specific docking tools, an independently constructed benchmark data set is urgently needed. Here we present the LEADS-PEP benchmark data set for assessing peptide docking performance. Using a rational and unbiased workflow, 53 protein-peptide complexes with peptide lengths ranging from 3 to 12 residues were selected. The data set is publicly accessible at www.leads-x.org. In a second step we evaluated several small molecule docking programs for their potential to reproduce peptide conformations as present in LEADS-PEP. While most tested programs were capable to generate native-like binding modes of small peptides, only Surflex-Dock and AutoDock Vina performed reasonably well for peptides consisting of more than five residues. Rescoring of docking poses with scoring functions ChemPLP, ChemScore, and ASP further increased the number of top-ranked near-native conformations. Our results suggest that small molecule docking programs are a good and fast alternative to specialised peptide docking programs.