以特异性噬菌体为靶进行配基筛选的分子模建及活性鉴定  

Computer-aided molecular modeling and activity estimation for ligand screening with specific phage clone as the target

作　　者：罗海波[1] 胡远东[2] 刘北一[1] 李松[2] 富宁[1] 

机构地区：[1]南方医科大学免疫学教研室,广东广州510515 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《南方医科大学学报》2007年第8期1127-1131,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(30471550);广东省自然科学基金(32877)~~

摘　　要：目的利用计算机辅助分子模拟技术,分析TNF模拟序列与配基的结合。方法利用计算机模建,对特异性模拟TNF的环七肽单表位克隆LCS-7(c-RRPAQSG-c)与以其为靶筛选获得的配基即TNFα结合肽LLT-18(EHMALTYPFRPP)及TNFα分子间相互结合作用进行分子模拟分析;并合成LLT-18进行ELISA鉴定与验证。结果和结论计算机模建分析显示LLT-18与TNFα表位模拟肽之间结合作用同其与TNFα分子间相互结合作用具有相似性;固相合成LLT-18短肽可与TNFα结合,证明了以噬菌体为靶进行配基筛选及分子模建预测小分子肽相互作用的可行性。To investigate the interaction between tumor necrosis factor α （TNFα） mimotopes and TNFα-binding peptides screened from random phage display peptide library with TNFα mimotopes displayed on phage clone as the target, the computational docking program AutoDock （with confirmation calculations using Discover） was used to predict and analyze the binding modes of LLT-18 （TNFα binding peptide, sequence EHMALTYPFRPP） with TNFα, after which LCS-7 （TNFα mimic phage clone, displayed positive sequence c-RRPAQSG-c） was docked to LLT-18 manually. The binding between LLT-18 and TNFα or LCS-7 was stabilized predominantly through electrostatic interaction and H-bond formation. The Arg residues in TNFα or LCS-7 were important for their interaction with LLT- 18. For LLT- 18, the key amino acid residues were Glu 1, His2, Met3 and Tyr7. These results suggest the feasibility of screening ligand to single epitope with specific phage clone as the target, and of predicting the interaction between small peptides by computer-aided molecular modeling.

关 键 词：同源模建 噬菌体 TNFΑ 单表位 结合肽 

分 类 号：R346[医药卫生—基础医学]