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Stepwise identification of HLA‐A*0201‐restricted CD8 + T‐cell epitope peptides from herpes simplex virus type 1 genome boosted by a steprank scheme
Author(s) -
Bi Jianjun,
Song Rengang,
Yang Huilan,
Li Bingling,
Fan Jianyong,
Liu Zhongrong,
Long Chaoqin
Publication year - 2010
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21564
Subject(s) - epitope , herpes simplex virus , chemistry , human leukocyte antigen , virology , genome , identification (biology) , cd8 , virus , computational biology , antigen , biology , gene , genetics , biochemistry , botany
Identification of immunodominant epitopes is the first step in the rational design of peptide vaccines aimed at T‐cell immunity. To date, however, it is yet a great challenge for accurately predicting the potent epitope peptides from a pool of large‐scale candidates with an efficient manner. In this study, a method that we named StepRank has been developed for the reliable and rapid prediction of binding capabilities/affinities between proteins and genome‐wide peptides. In this procedure, instead of single strategy used in most traditional epitope identification algorithms, four steps with different purposes and thus different computational demands are employed in turn to screen the large‐scale peptide candidates that are normally generated from, for example, pathogenic genome. The steps 1 and 2 aim at qualitative exclusion of typical nonbinders by using empirical rule and linear statistical approach, while the steps 3 and 4 focus on quantitative examination and prediction of the interaction energy profile and binding affinity of peptide to target protein via quantitative structure‐activity relationship (QSAR) and structure‐based free energy analysis. We exemplify this method through its application to binding predictions of the peptide segments derived from the 76 known open‐reading frames (ORFs) of herpes simplex virus type 1 (HSV‐1) genome with or without affinity to human major histocompatibility complex class I (MHC I) molecule HLA‐A*0201, and find that the predictive results are well compatible with the classical anchor residue theory and perfectly match for the extended motif pattern of MHC I‐binding peptides. The putative epitopes are further confirmed by comparisons with 11 experimentally measured HLA‐A*0201‐restrcited peptides from the HSV‐1 glycoproteins D and K. We expect that this well‐designed scheme can be applied in the computational screening of other viral genomes as well. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 328–339, 2011.