title: Knowledge-based virtual screening of HLA-A*0201-restricted CD8+ T-cell epitope peptides from herpes simplex virus genome.
abstract: 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.
authors.affiliation: Department of Dermatology, General Hospital of Guangzhou Military Command of PLA, Guangzhou, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Bi
authors.forename: Huilan
authors.initials: H
authors.lastname: Yang
authors.forename: Huacheng
authors.initials: H
authors.lastname: Yan
authors.forename: Rengang
authors.initials: R
authors.lastname: Song
authors.forename: Jianyong
authors.initials: J
authors.lastname: Fan
mesh_terms: D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002138:Calibration; D018360:Crystallography, X-Ray; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D016679:Genome, Viral / Q000235:genetics*; D015234:HLA-A Antigens / Q000737:chemistry / Q000276:immunology*; D015789:HLA-A2 Antigen; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000276:immunology; D019359:Knowledge; D016014:Linear Models; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D010455:Peptides / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D013816:Thermodynamics; D014584:User-Computer Interface; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides; D014764:Viral Proteins