On the usefulness of ion-mobility mass spectrometry and SAXS data in scoring docking decoys
On the usefulness of ion-mobility mass spectrometry and SAXS data in scoring docking decoys
复制标题
DOI：
10.1107/s0907444913007063
复制
发表时间：
2013-05-01
影响因子：
2.2
通讯作者：
Bonvin, Alexandre M. J. J.
中科院分区：
文献类型：
--
作者：
Karaca, Ezgi;Bonvin, Alexandre M. J. J.
评分，即从生成的构象池中选择生物相关的溶液的过程，是生物分子对接领域的主要挑战之一。应对这一挑战的一个突出方法是将基于信息的术语纳入评分功能。在这种情况下，从离子迁移率质谱仪(IM-MS)或SAXS实验获得的低分辨率形状数据已被集成到信息驱动对接程序HADDOK的常规评分功能中。在这里，系统地评估了基于IM-MS的评分和基于SAXS的评分的优势和劣势，无论是单独使用还是与黑线鳕评分结合使用。对在从头算模式下运行黑线鳕产生的二聚体组成的大型对接诱饵集的分析结果表明，IM-MS数据的内容对于选择正确的模型来说分辨率太低，而使用SAXS数据进行评分可以显著提高性能。然而，SAXS评分的有效性取决于复合体的形状和排列，其中长圆形和扁平系统表现最佳。观察到，当SAXS评分与基于能量的黑线鳕评分相结合时，准确率最高。
Scoring, the process of selecting the biologically relevant solution from a pool of generated conformations, is one of the major challenges in the field of biomolecular docking. A prominent way to cope with this challenge is to incorporate information-based terms into the scoring function. Within this context, low-resolution shape data obtained from either ion-mobility mass spectrometry (IM-MS) or SAXS experiments have been integrated into the conventional scoring function of the information-driven docking program HADDOCK. Here, the strengths and weaknesses of IM-MS-based and SAXS-based scoring, either in isolation or in combination with the HADDOCK score, are systematically assessed. The results of an analysis of a large docking decoy set composed of dimers generated by running HADDOCK in ab initio mode reveal that the content of the IM-MS data is of too low resolution for selecting correct models, while scoring with SAXS data leads to a significant improvement in performance. However, the effectiveness of SAXS scoring depends on the shape and the arrangement of the complex, with prolate and oblate systems showing the best performance. It is observed that the highest accuracy is achieved when SAXS scoring is combined with the energy-based HADDOCK score.