Knowledge-based virtual screening of HLA-A*0201-restricted CD8+ T-cell epitope peptides from herpes simplex virus genome
Knowledge-based virtual screening of HLA-A*0201-restricted CD8+ T-cell epitope peptides from herpes simplex virus genome
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DOI：
10.1016/j.jtbi.2011.04.018
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发表时间：
2011-07-21
影响因子：
2
通讯作者：
Fan, Jianyong
中科院分区：
文献类型：
--
作者：
Bi, Jianjun;Yang, Huilan;Fan, Jianyong
开发了一种新的基于知识的方法，从大规模肽候选物中虚拟筛选潜在的HLA-A*0201结合剂。该方法利用来自与HLA-A*0201结合的各种肽的晶体结构和实验亲和力的信息来构建用于准确表征HLA-A*0201-肽相互作用和用于有效预测肽与HLA-A*0201的结合亲和力的单位置突变自由能谱。我们采用这种方法来分析的物理化学性质和结构的影响，潜在的特异性识别和关联之间的HLA-A*0201和一个大面板的肽段产生的单纯疱疹病毒1型（HSV-1）基因组，并评估这些肽候选人的结合效力HLA-A*0201。结果，38，020个候选物中的288个被预测为HLA-A*0201的潜在高亲和力结合物，从中挑选出三个最有希望的肽用于进一步开发针对HSV-1的有效疫苗。此外，我们还证明了这种新提出的方法可以成功地从HSV-1的糖蛋白D和K中鉴定出8种已知的结合物和3种已知的非结合物。(C)2011爱思唯尔有限公司保留所有权利。
A novel knowledge-based method is developed to virtually screen potential HLA-A*0201 binders from large-scale peptide candidates. This method utilizes the information from both the crystal structures and experimental affinities of various peptides bound with HLA-A*0201 to construct a single-position mutation free energy profile for accurately characterizing HLA-A*0201-peptide interaction and for effectively predicting the binding affinities of peptides to HLA-A*0201. We employ this method to analyze physicochemical properties and structural implication underlying the specific recognition and association between the HLA-A*0201 and a large panel of peptide segments generated from the herpes simplex virus type 1 (HSV-1) genome, and to evaluate the binding potencies of these peptide candidates to HLA-A*0201. As a result, 288 out of 38,020 candidates are predicted as the potential high-affinity binders of HLA-A*0201, from which three most promising peptides are picked out for further development of potent vaccines against HSV-1. In addition, we also demonstrate that this newly proposed method can successfully identify 8 known binders and 3 known nonbinders from the glycoproteins D and K of HSV-1. (C) 2011 Elsevier Ltd. All rights reserved.