Predicting oligomeric assemblies:: N-mers a primer
Predicting oligomeric assemblies:: N-mers a primer
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DOI：
10.1016/j.jsb.2005.03.006
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发表时间：
2005-06-01
影响因子：
3
通讯作者：
Camacho, CJ
中科院分区：
文献类型：
--
作者：
Comeau, SR;Camacho, CJ
多蛋白质复合体在许多生物过程中起着关键作用。然而，由于这些组件的结构很难通过实验解决，它们如何在细胞内协同工作的详细机制仍然难以捉摸。同样，最近在蛋白质-蛋白质相互作用的电子预测方面的进展到目前为止避免了这个难题。在这篇文章中，我们提出了一个通用的算法来预测均低聚物的分子组装。给定N-MERS的数量和一个单体的3D结构，该方法对N-MERS可以组装的所有可能的对称性进行采样。基于对每个结合界面上的低自由能结构进行聚类的评分函数，该算法预测了蛋白质组装的复杂结构和对称性。该方法是非常通用的，不涉及任何自由参数。该算法已作为公共服务器实现，并集成到蛋白质-蛋白质复合体预测服务器ClusPro中。使用这一应用程序，我们验证了总共107个组件的三聚体、四聚体(区分二聚体和四重对称结构)、五聚体和六聚体(区分二聚体的三聚体、三聚体的二聚体和6重对称结构)的预测。对于85%)的多聚体，服务器预测与全晶体的平均RMS偏差在2埃内的复杂结构。对于涉及一个以上结合界面的络合物，每个表面的团簇大小提供了一个强烈的指示，表明哪个界面首先形成。随着评分功能和计算机能力的提高，我们的多聚体对接方法可以作为一个框架来解决更普遍的多蛋白质组装问题。(C)2005 Elsevier Inc.保留所有权利。
Multi-protein complexes play key roles in many biological processes. However, since the structures of these assemblies are hard to resolve experimentally, the detailed mechanism of how they work cooperatively in the cell has remained elusive. Similarly, recent advances on in silico prediction of protein-protein interactions have so far avoided this difficult problem. In this paper, we present a general algorithm to predict molecular assemblies of homo-oligomers. Given the number of N-mers and the 3D structure of one monomer, the method samples all the possible symmetries that N-mers can be assembled. Based on a scoring function that clusters the low free energy structures at each binding interface, the algorithm predicts the complex structure as well as the symmetry of the protein assembly. The method is quite general and does not involve any free parameters. The algorithm has been implemented as a public server and integrated to the protein-protein complex prediction server ClusPro. Using this application, we validated predictions for trimers, tetramers (discriminating between dimer of dimers and 4-fold symmetry structures), pentamers and hexamers (discriminating between trimer of dimers, dimer of trimers, and 6-fold symmetry structures), for a total of 107 assemblies. For 85%) of the multimers, the server predicts the complex structure within an average rms deviation of 2 angstrom from the full crystal. For complexes that involve more than one binding interface, the cluster size at each surface provides a strong indication as to which interface forms first. With improving scoring functions and computer power, our multimer docking approach could be used as a framework to address the more general problem of multi-protein assemblies. (c) 2005 Elsevier Inc. All rights reserved.