Doppelt-Azeroual Olivia, Moriaud Fabrice, Delfaud François, de Brevern Alexandre G
MEDIT SA, 2 rue du Belvédère, Palaiseau, France.
Drug Des Devel Ther. 2009 Sep 21;3:59-72. doi: 10.2147/dddt.s4706.
Three-dimensional structural information is critical for understanding functional protein properties and the precise mechanisms of protein functions implicated in physiological and pathological processes. Comparison and detection of protein binding sites are key steps for annotating structures with functional predictions and are extremely valuable steps in a drug design process. In this research area, MED-SuMo is a powerful technology to detect and characterize similar local regions on protein surfaces. Each amino acid residue's potential chemical interactions are represented by specific surface chemical features (SCFs). The MED-SuMo heuristic is based on the representation of binding sites by a graph structure suitable for exploration by an efficient comparison algorithm. We use this approach to analyze one particular SCOP superfamily which includes HSP90 chaperone, MutL/DNA topoisomerase, histidine kinases, and alpha-ketoacid dehydrogenase kinase C (BCK). They share a common fold and a common region for ATP-binding. To analyze both similar and differing features of this fold, we use a novel classification method, the MED-SuMo multi approach (MED-SMA). We highlight common and distinct features of these proteins. The different clusters created by MED-SMA yield interesting observations. For instance, one cluster gathers three types of proteins (HSP90, topoisomerase VI, and BCK) which all bind the drug radicicol.
三维结构信息对于理解蛋白质的功能特性以及蛋白质在生理和病理过程中发挥功能的精确机制至关重要。蛋白质结合位点的比较和检测是通过功能预测对结构进行注释的关键步骤，也是药物设计过程中极其有价值的步骤。在这个研究领域，MED-SuMo是一种用于检测和表征蛋白质表面相似局部区域的强大技术。每个氨基酸残基的潜在化学相互作用由特定的表面化学特征（SCF）表示。MED-SuMo启发式方法基于通过适合高效比较算法探索的图结构来表示结合位点。我们使用这种方法来分析一个特定的SCOP超家族，其中包括HSP90伴侣蛋白、MutL/DNA拓扑异构酶、组氨酸激酶和α-酮酸脱氢酶激酶C（BCK）。它们具有共同的折叠结构和ATP结合的共同区域。为了分析这种折叠结构的相似和不同特征，我们使用了一种新颖的分类方法，即MED-SuMo多方法（MED-SMA）。我们突出了这些蛋白质的共同和独特特征。MED-SMA创建的不同簇产生了有趣的观察结果。例如，一个簇聚集了三种类型的蛋白质（HSP90、拓扑异构酶VI和BCK），它们都与药物萝卜硫素结合。
