文献类型：期刊文献

中文题名：多肽组学联合分子对接筛选玉足海参抗血栓肽

英文题名：Peptidomics combined with molecular docking screening for antithrombotic peptides from sea cucumber(Holothuria leucospilota)

作者：李汉琪[1];王治军[1];郑清瑶[1];宋春勇[1];陈忠琴[1,2];谭明堂[1,2];林海生[1,2];曹文红[1,2]

机构：[1]广东海洋大学食品科技学院,国家贝类加工技术研发分中心(湛江),广东省水产品加工与安全重点实验室,广东省海洋食品工程技术研究中心,广东省海洋生物制品工程实验室,广东湛江524088;[2]海洋食品精深加工关键技术省部共建协同创新中心,大连工业大学,辽宁大连116034

年份：2024

卷号：50

期号：20

起止页码：104

中文期刊名：食品与发酵工业

外文期刊名：Food and Fermentation Industries

收录：北大核心2023、CSTPCD、、Scopus、CSCD2023_2024、北大核心、CSCD

基金：“十三五”国家重点研发计划重点专项(2020YFD0901104);湛江市农业技术攻关项目(2021A05187)。

语种：中文

中文关键词：玉足海参;多肽组学;生物信息学;分子对接;抗血栓肽

外文关键词：sea cucumber(Holothuria leucospilota);peptidomics;bioinformatics;molecular docking;antithrombotic peptide

中文摘要：基于多肽组学联合分子对接技术筛选玉足海参来源的具有抗血栓作用的活性肽。采用LC-MS/MS技术表征玉足海参酶解液全肽谱,通过简易分离纯化建立小规模的候选肽库,同时借助生物信息学软件对多肽库进行理化性质分析,评估抗血栓活性筛选方法的可行性;利用Discovery Studio软件以重组水蛭素片段(HIRV2)与凝血酶的结合模式,进行分子对接筛选潜在抗血栓肽序列,以部分凝血活酶时间、凝血酶原时间、凝血酶时间及凝血酶抑制率4项指标评估人工合成肽的抗血栓活性。结果表明,玉足海参酶解液含有1 795条肽序列。选取相对分子质量为1~3 kDa的116条肽序列建立候选肽库,分子对接筛选出6种潜在的抗血栓活性肽(CDOCKER ENERGY均高于HIRV2)。其中SCp-1和SCp-2分别与凝血酶的10个氨基酸残基位点紧密结合,表明它们是潜在的抗血栓活性肽。体外活性表明,SCp-1和SCp-2均呈剂量依赖趋势的内源性抗凝活性以及共同通路的抗凝活性(P<0.05),二者相较下SCp-1在内源性通路抗凝能力较强,SCp-2则在共同通路表现出更好的抗凝活性。综上,通过多肽组学联合分子对接成功从玉足海参酶解产物中筛选获得2种新型食源性抗血栓肽。

外文摘要：Based on peptidomics combined with molecular docking technology,active peptides with antithrombotic effects were screened from Holothuria leucospilota.LC-MS/MS technology was used to characterize the full peptide spectrum of the enzymatic hydrolysate of sea cucumber,and a small-scale candidate peptide library was established through simple separation and purification.At the same time,bioinformatics software was used to analyze the physicochemical properties of the peptide library and evaluate the feasibility of the anti-thrombotic activity screening method.Using Discovery Studio software to screen potential antithrombotic peptide sequences by molecular docking based on the binding mode of recombinant hirudin fragment(HIRV2)and thrombin,the antithrombotic activity of artificially synthesized peptides was evaluated using four indicators,including activated partial thromboplatin time,prothrombin time,thrombin time,and thrombin inhibition rate.Results showed that the enzymatic hydrolysate of sea cucumber contained 1795 peptide sequences.116 peptide sequences with a relative molecular weight of 1-3 kDa were selected to establish a candidate peptide library.Six potential antithrombotic active peptides(CDOCKER ENERGY was higher than HIRV2)were screened through molecular docking.SCp-1 and SCp-2 were closely bound to the 10 amino acid residues of thrombin,indicating that they were potential antithrombotic peptides.In vitro activity showed that both SCp-1 and SCp-2 exhibited(P<0.05)a dose-dependent endogenous anticoagulant activity and a common pathway anticoagulant activity.Compared to the two,SCp-1 exhibited stronger anticoagulant activity in the endogenous pathway,while SCp-2 exhibited better anticoagulant activity in the common pathway.In summary,two novel foodborne antithrombotic peptides were successfully screened from the enzymatic hydrolysis products of sea cucumber through peptide omics combined with molecular docking.