SymmRef: A flexible refinement method for symmetric multimers
SymmRef: A flexible refinement method for symmetric multimers
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DOI：
10.1002/prot.23082
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发表时间：
2011-09-01
影响因子：
2.9
通讯作者：
Wolfson, Haim J.
中科院分区：
文献类型：
--
作者：
Mashiach-Farkash, Efrat;Nussinov, Ruth;Wolfson, Haim J.
对称蛋白复合物在活细胞中大量存在。预测它们的原子结构可以揭示许多重要生物过程的机制。对称对接方法的目的是在给定单体或其模型的未结合结构的情况下预测这些配合物的结构。与不对称的蛋白质-蛋白质对接相比，对称约束减少了这些方法的搜索空间，使预测更容易。然而，对单体可能经历的构象变化进行建模的挑战是一个主要障碍。在本文中，我们提出了一种新的对称对接解的改进和重新排序方法SymmRef。该方法模拟了主链和侧链运动，并优化了单体的刚体取向。主链运动采用正态模态最小化建模，侧链构象采用最优转子选择建模。由于求解的对称多聚体结构显示不对称侧链构象，因此我们在侧链优化过程中不使用对称约束。改进后的模型根据能量评分重新排序。我们在未绑定对接挑战的基准测试中测试了该方法。结果表明，该方法显著提高了对称刚性对接解的精度和排序。SymmRef可从http://bioinfo3d.cs.tau.ac.il/SymmRef/download.html下载。
Symmetric protein complexes are abundant in the living cell. Predicting their atomic structure can shed light on the mechanism of many important biological processes. Symmetric docking methods aim to predict the structure of these complexes given the unbound structure of a single monomer, or its model. Symmetry constraints reduce the search-space of these methods and make the prediction easier compared to asymmetric protein-protein docking. However, the challenge of modeling the conformational changes that the monomer might undergo is a major obstacle. In this article, we present SymmRef, a novel method for refinement and reranking of symmetric docking solutions. The method models backbone and side-chain movements and optimizes the rigid-body orientations of the monomers. The backbone movements are modeled by normal modes minimization and the conformations of the side-chains are modeled by selecting optimal rotamers. Since solved structures of symmetric multimers show asymmetric side-chain conformations, we do not use symmetry constraints in the side-chain optimization procedure. The refined models are re-ranked according to an energy score. We tested the method on a benchmark of unbound docking challenges. The results show that the method significantly improves the accuracy and the ranking of symmetric rigid docking solutions. SymmRef is available for download at http://bioinfo3d.cs.tau.ac.il/SymmRef/download.html.