Identification of protein-protein interaction sites from docking energy landscapes
Identification of protein-protein interaction sites from docking energy landscapes
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DOI：
10.1016/j.jmb.2003.10.069
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发表时间：
2004-01-16
影响因子：
5.6
通讯作者：
Abagyan, R
中科院分区：
文献类型：
--
作者：
Fernández-Recio, J;Totrov, M;Abagyan, R
蛋白质识别是结构生物学中最具挑战性和最有趣的问题之一。尽管有关于蛋白质-蛋白质复合物的所有可用的结构、序列和生物物理信息，但使蛋白质表面可能参与蛋白质-蛋白质相互作用的物理化学模式（如果有的话）仍然难以捉摸。在这里，我们应用蛋白质对接模拟和相互作用能量景观分析来确定蛋白质-蛋白质相互作用位点。基于配体全原子模型的多起点全局能量优化的全局对接新方案，在24个配合物的训练集上优化了详细的受体电位和原子溶剂化参数，不受限制地探索了整个受体周围的构象空间。通过模拟生成的刚体对接解的集合随后被用于将对接能量景观投影到蛋白质表面。我们发现密集的低能区与实际的结合位点一致。该程序在21个已知蛋白质-蛋白质复合物的测试集上进行了验证，该测试集未在训练集中使用。高达81%的预测高倾向斑块残基正确定位在原生界面上。这种方法可以指导蛋白质表面突变的设计，提供可能相互作用的几何细节，并有助于在结构蛋白质组学中注释蛋白质表面。(C) 2003 Elsevier Ltd.版权所有。
Protein recognition is one of the most challenging and intriguing problems in structural biology. Despite all the available structural, sequence and biophysical information about protein-protein complexes, the physico-chemical patterns, if any, that make a protein surface likely to be involved in protein-protein interactions, remain elusive. Here, we apply protein docking simulations and analysis of the interaction energy landscapes to identify protein-protein interaction sites. The new protocol for global docking based on multi-start global energy optimization of an allatom model of the ligand, with detailed receptor potentials and atomic solvation parameters optimized in a training set of 24 complexes, explores the conformational space around the whole receptor without restrictions. The ensembles of the rigid-body docking solutions generated by the simulations were subsequently used to project the docking energy landscapes onto the protein surfaces. We found that highly populated low-energy regions consistently corresponded to actual binding sites. The procedure was validated on a test set of 21 known protein-protein complexes not used in the training set. As much as 81% of the predicted high-propensity patch residues were located correctly in the native interfaces. This approach can guide the design of mutations on the surfaces of proteins, provide geometrical details of a possible interaction, and help to annotate protein surfaces in structural proteomics. (C) 2003 Elsevier Ltd. All rights reserved.