Department of Biological Sciences , Institute for Advanced Studies in Basic Sciences (IASBS) , Zanjan , 45137-66731 , Iran.
J Chem Inf Model. 2018 Mar 26;58(3):733-745. doi: 10.1021/acs.jcim.7b00606. Epub 2018 Feb 26.
Protein complexes play deterministic roles in live entities in sensing, compiling, controlling, and responding to external and internal stimuli. Thermodynamic stability is an important property of protein complexes; having knowledge about complex stability helps us to understand the basics of protein assembly-related diseases and the mechanism of protein assembly clearly. Enormous protein-protein interactions, detected by high-throughput methods, necessitate finding fast methods for predicting the stability of protein assemblies in a quantitative and qualitative manner. The existing methods of predicting complex stability need knowledge about the three-dimensional (3D) structure of the intended protein complex. Here, we introduce a new method for predicting dissociation free energy of subunits by analyzing the structural and topological properties of a protein binding patch on a single subunit of the desired protein complex. The method needs the 3D structure of just one subunit and the information about the position of the intended binding site on the surface of that subunit to predict dimer stability in a classwise manner. The patterns of structural and topological properties of a protein binding patch are decoded by recurrence quantification analysis. Nonparametric discrimination is then utilized to predict the stability class of the intended dimer with accuracy greater than 85%.
蛋白质复合物在生命体中发挥着确定性作用，用于感知、编译、控制和响应外部和内部刺激。热力学稳定性是蛋白质复合物的一个重要性质；了解复合物的稳定性有助于我们清楚地理解与蛋白质组装相关疾病的基础和蛋白质组装的机制。通过高通量方法检测到大量的蛋白质-蛋白质相互作用，这就需要找到快速的方法，以定量和定性的方式预测蛋白质组装体的稳定性。现有的预测复合物稳定性的方法需要关于目标蛋白质复合物的三维（3D）结构的知识。在这里，我们通过分析目标蛋白质复合物的单个亚基上的蛋白质结合斑的结构和拓扑性质，介绍了一种预测亚基解离自由能的新方法。该方法仅需要一个亚基的 3D 结构和该亚基表面上预期结合位点的位置信息，就可以分类预测二聚体的稳定性。蛋白质结合斑的结构和拓扑性质模式通过递归定量分析进行解码。然后利用非参数判别来预测目标二聚体的稳定性类别，准确率超过 85%。
