磷脂生物代谢网络的对接重构计算

Detailed docking of “phospholipid” biological metabolizing pathway

目的:拟在分析蛋白的功能聚类和体内作用基础上,建立生物体内蛋白质的生理功能相关网络,相关研究结果有助于在基于整体生物学功能理解的基础上做出正确的选择。方法:通过多重对接策略构建生物功能网络,采用受体-配体相互作用强度分子指纹图谱揭示蛋白质未知的生物学功能以及它们之间的联系。结果:对包含27个蛋白酶和28个内源性生物活性分子的磷脂代谢网络进行了重构计算,从蛋白质–配基作用网络的重构和基于生物网络的分子设计两个方面研究了直接相互作用方法在实际生物体系中的有效性。结论:对于弱相互作用的生物体系,通过多次平行的对接计算和聚类分析方法可达到有效的排名和认定真正存在的相互作用的目的;本研究所建立的基于多重对接和受体-配体相互作用强度指纹图谱的生物网络重构计算策略可进一步作为一类有效的工具,广泛应用在蛋白质分类、靶标选择和抑制剂的设计中。

Objective: To construct protein functional network according to the physiological process in vivo and functionally based distinct families, to understand biological functions, and to make wise decisions. Methods: We described here a very effective strategy combining with multiple-docking and protein-ligand binding-affinity fingerprint method to generate bio-functional network and pathway and reveal the protein 'unknown' functions and their relationship. Results: Totally 27 sets of proteins and 28 bio-active molecules were used to reconstruct the possible phospholipids metabolic network by computational simulation strategy. The protein-ligand network reconstruction and pathway based drug design showed that the direct interaction investigation might be effective in complex biological system study. Conclusion: Even for weak and moderate interactions in the real biology system, the relationship between each other can be achieved by fingerprint analysis based on multiple-docking data. The results of these calculations give valuable insight into the pathway and the function relationship among these proteins. This method can be a very useful tool for protein classification, target selection, and inhibitor design.