Prediction of promiscuous and high-affinity mutated MHC binders
Prediction of promiscuous and high-affinity mutated MHC binders
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DOI：
10.1089/153685903322328956
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发表时间：
2003-08-01
期刊：
影响因子：
--
通讯作者：
Raghava, GPS
中科院分区：
文献类型：
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作者：
Bhasin, M;Raghava, GPS
在抗原序列中识别能够与多种MHC等位基因高亲和力结合的多肽是亚单位疫苗设计中的挑战之一。天然多肽的突变是获得能与多种MHC等位基因高亲和力结合的多肽的一种替代方法。为了确定定义高亲和力结合肽的突变，通常需要进行大量的实验。因此，有必要开发一种计算方法来检测多肽中的氨基酸突变，以使其成为高亲和力或混杂的MHC结合。这份报告描述了一种高通量的计算机驱动的解决方案，通过在抗原序列中引入突变来识别47个MHC I类等位基因的混杂和高亲和力突变的结合。该方法实现了用于在抗原序列中创建最佳突变的定量矩阵。它有两个主要选项：(I)预测混杂的MHC结合剂和(Ii)预测高亲和力结合剂。在预测混杂结合的情况下，服务器允许用户选择(I)肽中允许的突变；(Ii)它应该与之结合的MHC等位基因；以及(Iii)允许突变的位置。在预测高亲和力结合蛋白的情况下，服务器允许用户指定应该在天然蛋白质中保守的位置。在这两种情况下，该方法都会计算获得所需结果所需的9-聚肽的突变类型和突变位置。网络服务器NIMBPred的网址为www.imtech.res.in/raghava/mmbpre/。
The identification of peptides in an antigenic sequence that can bind with high affinity to a wide range of MHC alleles is one of the challenges in subunit vaccine design. The mutation of natural peptides is an alternative to obtaining peptides that can bind to a wide range of MHC alleles with high affinity. A large number of experiments are typically necessary to identify mutations that define high-affinity binding peptides. Therefore there is a need to develop a computational method for detecting amino acid mutations in a peptide for making it high-affinity or promiscuous MHC binders. This report describes a high-throughput computer driven solution for the identification of promiscuous and high-affinity mutated binders of 47 MHC class I alleles by introducing mutations in an antigenic sequence. The method implements quantitative matrices for creating optimal mutations in an antigenic sequence. It has two major options: (i) prediction of promiscuous MHC binders and (ii) prediction of high-affinity binders. In case of prediction of promiscuous binders, the server allows a user to select (i) permissible mutations in a peptide; (ii) MHC alleles to whom it should bind; and (iii) positions at which mutation is allowed. In the case of prediction of high-affinity binders, the server allows users to specify the positions that should be conserved in the native protein. In both cases, the method computes the type of mutations and position of mutations in 9-mer peptides required to have the desired results. The web server NIMBPred is available at www.imtech.res.in/raghava/mmbpre/.