Biozentrum, University of Basel, Basel 4056, Switzerland.
SIB Swiss Institute of Bioinformatics, Basel 4056, Switzerland.
Bioinformatics. 2020 Mar 1;36(6):1765-1771. doi: 10.1093/bioinformatics/btz828.
MOTIVATION: Methods that estimate the quality of a 3D protein structure model in absence of an experimental reference structure are crucial to determine a model's utility and potential applications. Single model methods assess individual models whereas consensus methods require an ensemble of models as input. In this work, we extend the single model composite score QMEAN that employs statistical potentials of mean force and agreement terms by introducing a consensus-based distance constraint (DisCo) score. RESULTS: DisCo exploits distance distributions from experimentally determined protein structures that are homologous to the model being assessed. Feed-forward neural networks are trained to adaptively weigh contributions by the multi-template DisCo score and classical single model QMEAN parameters. The result is the composite score QMEANDisCo, which combines the accuracy of consensus methods with the broad applicability of single model approaches. We also demonstrate that, despite being the de-facto standard for structure prediction benchmarking, CASP models are not the ideal data source to train predictive methods for model quality estimation. For performance assessment, QMEANDisCo is continuously benchmarked within the CAMEO project and participated in CASP13. For both, it ranks among the top performers and excels with low response times. AVAILABILITY AND IMPLEMENTATION: QMEANDisCo is available as web-server at https://swissmodel.expasy.org/qmean. The source code can be downloaded from https://git.scicore.unibas.ch/schwede/QMEAN. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
动机:在缺乏实验参考结构的情况下,估计 3D 蛋白质结构模型质量的方法对于确定模型的实用性和潜在应用至关重要。单模型方法评估单个模型,而共识方法则需要模型集合作为输入。在这项工作中,我们通过引入基于共识的距离约束(DisCo)评分扩展了使用平均力统计势和一致性项的单模型复合评分 QMEAN。
结果:DisCo 利用与正在评估的模型具有同源性的实验确定的蛋白质结构的距离分布。前馈神经网络经过训练,可以自适应地加权多模板 DisCo 评分和经典单模型 QMEAN 参数的贡献。结果是复合评分 QMEANDisCo,它结合了共识方法的准确性和单模型方法的广泛适用性。我们还证明,尽管 CASP 模型是结构预测基准测试的事实上的标准,但它们并不是训练模型质量估计预测方法的理想数据源。为了进行性能评估,QMEANDisCo 持续在 CAMEO 项目中进行基准测试,并参与了 CASP13。在这两个项目中,它都位列表现最佳者之列,并且具有低响应时间的优势。
可用性和实现:QMEANDisCo 可在 https://swissmodel.expasy.org/qmean 上作为网络服务器使用。源代码可从 https://git.scicore.unibas.ch/schwede/QMEAN 下载。
补充信息:补充数据可在生物信息学在线获得。
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