Wiltgen Marco, Tilz Gernot P
Institute of Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
Hematology. 2008 Aug;13(4):224-9. doi: 10.1179/102453308X315988.
Inflammation of vessels is partially caused by tumour necrosis factor (TNF). Although the pharmacological understanding of the main inflammatory protein data is well characterised, basic structural information is rare. For this reason, we developed a method for the representation and analysis of the macromolecular interface between TNF and its receptor, enabling a better understanding of their interaction. In this paper we use structural information on the TNF-receptor complex in the protein (PDB) database as input to calculate an interface contact matrix, based on the distance between individual residues of each counterpart. The two-dimensional matrix is a plot of pairwise interactions between adjacent residues of the two chains in the protein complex. The residue names within each chain are plotted on the respective axis and an entry is made wherever two residues come into close contact. The matrix elements are annotated with physicochemical properties. The interface contact matrix is linked to a 3D visualisation of the macromolecular structure in such a way that mouse clicking on the appropriate part of the interface contact matrix highlights the corresponding residues in the 3D structure. Additionally the residues in the matrix are used to define the molecular surface at the interface. The interface contact matrix enables an overview representation of the residue distribution at the macromolecular interface and an evaluation of interfacial 'hot spots'. The selection of the residues in the interface contact matrix and the highlighting in the 3D structure allow an easy retrieval of the desired information out of the wealth of structural information. The representation with molecular surfaces shows complementary shapes. Many forms of treatment have been developed to reduce excessive TNF activity and their success is based on knowledge of the active sites of TNF. Our macromolecular interface analysis system will help us to define better receptor and acceptor molecules for the neutralisation and excretion of TNF.
血管炎症部分由肿瘤坏死因子（TNF）引起。尽管对主要炎症蛋白数据的药理学理解已得到充分表征，但基本结构信息却很少。因此，我们开发了一种方法来表示和分析TNF与其受体之间的大分子界面，以便更好地理解它们的相互作用。在本文中，我们将蛋白质（PDB）数据库中TNF受体复合物的结构信息作为输入，基于每个对应物中各个残基之间的距离来计算界面接触矩阵。二维矩阵是蛋白质复合物中两条链相邻残基之间成对相互作用的图谱。每条链内的残基名称绘制在各自的轴上，只要两个残基紧密接触就会有一个条目。矩阵元素用物理化学性质进行注释。界面接触矩阵与大分子结构的三维可视化相链接，使得在界面接触矩阵的适当部分进行鼠标点击会突出显示三维结构中的相应残基。此外，矩阵中的残基用于定义界面处的分子表面。界面接触矩阵能够对大分子界面处的残基分布进行概述表示，并评估界面“热点”。在界面接触矩阵中选择残基并在三维结构中突出显示，使得能够从大量结构信息中轻松检索所需信息。分子表面表示显示出互补形状。已经开发了多种治疗方法来降低过度的TNF活性，其成功基于对TNF活性位点的了解。我们的大分子界面分析系统将帮助我们更好地定义用于中和和排泄TNF的受体和受体分子。
