基于计算机辅助水解和蛋白互作网络的珍珠母寡肽作用机制解析(1)
[摘要] 珍珠母蛋白及活性肽是珍珠母發挥疗效的主要成分之一，解析其药效物质及作用机制具有重要研究意义。该研究利用计算机辅助水解和蛋白互作网络等模拟技术，获得珍珠母的活性寡肽成分，预测其潜在的作用靶标并解析珍珠母寡肽的作用机制。通过收集珍珠母的主要珍珠层蛋白序列，采用计算机辅助水解方法进行蛋白的模拟消化水解，构建了包含458条珍珠母水解寡肽的三维结构数据库。随后利用反向找靶技术预测珍珠母寡肽的作用靶点，并通过网络富集技术法对排名前20的关键靶点及其蛋白互作关系进行分析，获得12个功能模块。从系统角度理解各种生物学过程，发现珍珠母寡肽的作用靶点与神经系统相关疾病有密切关系，提示珍珠母寡肽具有能治疗中枢神经类相关疾病的功效。计算机辅助水解方法可以高效地对已知序列结构的珍珠母蛋白进行模拟水解，并结合蛋白互作网络，解析珍珠母寡肽治疗神经类疾病的作用机制。该研究为探讨中药寡肽类药效物质发现及作用机制解析的提供研究思路，为开展寡肽类中药设计研究提供了重要的技术支撑。
[关键词] 计算机辅助水解； 珍珠母； 蛋白互作网络； 反向找靶； 药效团； 寡肽
, 百拇医药
Pharmacological mechanism analysis of oligopeptide from Pinctada fucata
based on in silico proteolysis and protein interaction network
CHEN Yankun， QIAO Liansheng， HUO Xiaoqian， ZHANG Xu， HAN Na， ZHANG Yanling*
(School of Chinese Material Medica， Beijing University of Chinese Medicine， Beijing 100102， China)
[Abstract] Pinctada fucata oligopeptide is one of key pharmaceutical effective constituents of P. fucata. It is significant to analyze its pharmacological effect and mechanism. This study aims to discover the potential oligopeptides from P. fucata and analyze the mechanism of P. fucata oligopeptide based on in silico technologies and protein interaction network(PIN). First， main protein sequences of P. fucata were collected， and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then， key potential targets of P. fucata oligopeptides were obtained through pharmacophore screening. The proteinprotein interaction(PPI) of targets was achieved and implemented to construct PIN and analyze the mechanism of P. fucata oligopeptides. P. fucata oligopeptide database was constructed based on in silico technologies， including 458 oligopeptides. Twelve modules were identified from PIN by a graph theoretic clustering algorithm Molecular Complex Detection(MCODE) and analyzed by Gene ontology(GO) enrichment. The results indicated that P. fucata oligopeptides have an effect in treating neurological diseases， such as Alzheimer′s disease. In silico proteolysis could be used to analyze the protein sequences of traditional Chinese medicine(TCM). According to the combination of in silico proteolysis and PIN， the biological activity of oligopeptides could be interpreted rapidly based on the known TCM protein sequence. The study provides the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides.
[Key words] in silico proteolysis； Pinctada fucata； PIN； reverse target identification； pharmacophore； oligopeptides, 百拇医药(陈艳昆 乔连生 霍晓乾 张栩 韩娜 张燕玲)
[关键词] 计算机辅助水解； 珍珠母； 蛋白互作网络； 反向找靶； 药效团； 寡肽
, 百拇医药
Pharmacological mechanism analysis of oligopeptide from Pinctada fucata
based on in silico proteolysis and protein interaction network
CHEN Yankun， QIAO Liansheng， HUO Xiaoqian， ZHANG Xu， HAN Na， ZHANG Yanling*
(School of Chinese Material Medica， Beijing University of Chinese Medicine， Beijing 100102， China)
[Abstract] Pinctada fucata oligopeptide is one of key pharmaceutical effective constituents of P. fucata. It is significant to analyze its pharmacological effect and mechanism. This study aims to discover the potential oligopeptides from P. fucata and analyze the mechanism of P. fucata oligopeptide based on in silico technologies and protein interaction network(PIN). First， main protein sequences of P. fucata were collected， and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then， key potential targets of P. fucata oligopeptides were obtained through pharmacophore screening. The proteinprotein interaction(PPI) of targets was achieved and implemented to construct PIN and analyze the mechanism of P. fucata oligopeptides. P. fucata oligopeptide database was constructed based on in silico technologies， including 458 oligopeptides. Twelve modules were identified from PIN by a graph theoretic clustering algorithm Molecular Complex Detection(MCODE) and analyzed by Gene ontology(GO) enrichment. The results indicated that P. fucata oligopeptides have an effect in treating neurological diseases， such as Alzheimer′s disease. In silico proteolysis could be used to analyze the protein sequences of traditional Chinese medicine(TCM). According to the combination of in silico proteolysis and PIN， the biological activity of oligopeptides could be interpreted rapidly based on the known TCM protein sequence. The study provides the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides.
[Key words] in silico proteolysis； Pinctada fucata； PIN； reverse target identification； pharmacophore； oligopeptides, 百拇医药(陈艳昆 乔连生 霍晓乾 张栩 韩娜 张燕玲)