Automated Procedure for Contact-Map-Based Protein Structure Reconstruction
Automated Procedure for Contact-Map-Based Protein Structure Reconstruction
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DOI：
10.1007/s00232-014-9648-x
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发表时间：
2014-05-01
影响因子：
2.4
通讯作者：
Kotulska, Malgorzata
中科院分区：
文献类型：
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作者：
Konopka, Bogumil M.;Ciombor, Marika;Kotulska, Malgorzata
了解离子通道的三维结构可以使用生物物理模型对其传导性特征进行建模，并可以发现其细胞功能。最近的研究表明，使用蛋白质接触位点信息可以显著提高结构预测的质量。因此，人们提出了一系列基于接触图的蛋白质结构预测方法。由于用于验证的方法不同，它们的比较很困难。本文设计并验证了一种用于基于接触的蛋白质结构重构的接触式映射到结构管道(C2S_PIPELINE)。C2S管道可用于构建单体和多聚体蛋白质。在验证一组具有代表性的蛋白质结构时获得的结构的中位数RMSD等于5.27，并且重建了最好的结构，RMSD为1.59。在验证之后，对KCSA离子通道进行了详细的案例研究。根据接触点信息的不同部分，重建KCSA模型。获得的KCSA模型的结构特征分析得到了通道内静电势分布的透彻分析。研究表明，静电参数与模型的结构质量密切相关。因此，它们可以用来区分高质量和低质量的结构。我们发现，如果随机选择联系人，则需要30%的联系人信息来获得KCSA的准确结构。如果错误映射中剩余的触点或非触点被更改为相反的位置，则该数字将增加到70%。此外，研究还表明，局部重建精度与氨基酸参与的接触数有关。这导致结构核心中的重建精度高于外围区域。
Knowledge of the three-dimensional structures of ion channels allows for modeling their conductivity characteristics using biophysical models and can lead to discovering their cellular functionality. Recent studies show that quality of structure predictions can be significantly improved using protein contact site information. Therefore, a number of procedures for protein structure prediction based on their contact-map have been proposed. Their comparison is difficult due to different methodologies used for validation. In this work, a Contact Map-to-Structure pipeline (C2S_pipeline) for contact-based protein structure reconstruction is designed and validated. The C2S_pipeline can be used to reconstruct monomeric and multimeric proteins. The median RMSD of structures obtained during validation on a representative set of protein structures, equaled 5.27 , and the best structure was reconstructed with RMSD of 1.59 . The validation is followed by a detailed case study on the KcsA ion channel. Models of KcsA are reconstructed based on different portions of contact site information. Structural feature analysis of acquired KcsA models is supported by a thorough analysis of electrostatic potential distributions inside the channels. The study shows that electrostatic parameters are correlated with structural quality of models. Therefore, they can be used to discriminate between high and low quality structures. We show that 30 % of contact information is needed to obtain accurate structures of KcsA, if contacts are selected randomly. This number increases to 70 % in case of erroneous maps in which the remaining contacts or non-contacts are changed to the opposite. Furthermore, the study reveals that local reconstruction accuracy is correlated with the number of contacts in which amino acid are involved. This results in higher reconstruction accuracy in the structure core than peripheral regions.