Identification of discontinuous antigenic determinants on proteins based on shape complementarities
Identification of discontinuous antigenic determinants on proteins based on shape complementarities
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DOI：
10.1002/jmr.819
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发表时间：
2007-03-01
影响因子：
2.7
通讯作者：
Mayer, Bernd
中科院分区：
文献类型：
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作者：
Rapberger, Ronald;Lukas, Arno;Mayer, Bernd
鉴定蛋白质上抗原决定因素的各种程序已经开发出来，包括实验方法和计算方法。然而，这些技术大多集中在连续表位上，而对不连续表位的快速可靠的识别和验证仍然很少。在本文中，我们描述了一种用于检测蛋白质上不连续表位的计算工作流程。该工作流程使用给定的蛋白质3D结构作为输入，并将每个残基溶剂可及性约束与表位到副位形状的互补性措施和结合能相结合，用于在构象环境中分配抗原决定因子。我们开发了一套已知结构的26种抗原抗体复合物的程序，并通过生成虚拟旁位库进一步扩展了可用的旁位形状，以提高对构成不连续表位的候选残基的筛选。将该工作流程应用于26种已知具有不连续表位的抗原，结果正确识别了12个抗原-抗体相互作用位点的空间邻近性。结合溶剂可及性、形状互补性和结合能来识别不连续表位明显优于仅考虑可及性和残基距离约束的方法。版权所有(c) 2007约翰威利父子有限公司
Diverse procedures for identifying antigenic determinants on proteins have been developed, including experimental as well as computational approaches. However, most of these techniques focus on continuous epitopes, whereas fast and reliable identification and verification of discontinuous epitopes remains barely amenable.In this paper, we describe a computational workflow for the detection of discontinuous epitopes on proteins. The workflow uses a given protein 3D structure as input, and combines a per residue solvent accessibility constraint with epitope to paratope shape complementarity measures and binding energies for assigning antigenic determinants in the conformational context. We have developed the procedure on a given set of 26 antigen-antibody complexes with a known structure, and have further expanded the available paratope shapes by generating a virtual paratope library in order to improve the screening for candidate residues constituting discontinuous epitopes. Applying the workflow on the 26 given antigens with known discontinuous epitopes resulted in the correct identification of the spatial proximity of 12 antigen-anti body interaction sites. Combining solvent accessibility, shape complementarity and binding energies towards the identification of discontinuous epitopes clearly outperforms approaches solely considering accessibility and residue distance constraints. Copyright (c) 2007 John Wiley & Sons, Ltd.