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IMPACT OF COMPLEX FORMATION ON PREDICTING CONFORMATIONAL EPITOPES

机译:复杂形成对预测构象表象的影响

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摘要

Most conformational epitope (CE) prediction methods relyrnon the characteristics and geometrical conformations ofrnbound antigens. However, protein complex formation mayrncause conformational changes on antigens and lead tornvarious CE prediction results from an identical molecularrnantigen. To investigate the influence on flexible structures,rnthis article attempts to explore the impact of structuralrnchanges on the consistency of CE prediction from two wellknownrnprediction methods: SEPPA and DiscoTope. Theserntwo systems were adopted to evaluate the variation rate ofrnpredicted epitopes on two curated unbound/bound antigenrndatasets. The variation rate reflects the inconsistent level ofrnCE prediction between unbound/bound antigens, and thernexperimental results have shown that conformationallyrndeformed antigens give irregular prediction results,rnespecially when the molecular conformations are changedrnsignificantly. It is also observed that the loop segmentsrnwithin an antigen play a major role in structural variation torngive inconsistent CE prediction results for most availablernsystems. We suggest that a protein surface comparisonrnmodule based on deformation invariant features should bernanalyzed prior to CE prediction. The transition fromrnunbound to bound structures contributes convincingrnprediction results since the learning procedures of knownrnepitopes were obtained by extracting antigen structuresrnfrom complex formation datasets. This evaluation system,rnevaluated results, and curated database are freely accessiblernfrom .
机译:大多数构象表位(CE)预测方法取决于结合抗原的特征和几何构象。然而,蛋白质复合物的形成可能会导致抗原的构象变化,并导致来自相同分子抗原的不同CE预测结果。为了研究对柔性结构的影响,本文尝试通过两种著名的预测方法:SEPPA和DiscoTope探索结构变化对CE预测一致性的影响。这两个系统被用来评估两个策划的未结合/结合的抗原数据集上的预测表位的变异率。变化率反映了未结合/结合的抗原之间的rnCE预测水平不一致,并且实验结果表明,构象变形的抗原给出不规则的预测结果,尤其是当分子构象发生显着变化时。还观察到,对于大多数可用系统,抗原内的环片段在结构变异中导致CE预测结果不一致。我们建议在CE预测之前应先分析基于变形不变特征的蛋白质表面比较模块。由于从已知的表位的学习程序是通过从复杂的形成数据集中提取抗原结构而获得的,因此从无约束结构过渡到结合结构的结果令人信服。该评估系统,重新评估的结果和精选的数据库可从中免费访问。

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