Development of a novel in silico docking simulation model for the fine HIV-1 cytotoxic T lymphocyte epitope mapping

• Published in: PloS one 2012-07, Vol.7 (7), p.e41703-e41703
• Main Authors: Mori, Masahiko, Matsuki, Kei, Maekawa, Tomoyuki, Tanaka, Mari, Sriwanthana, Busarawan, Yokoyama, Masaru, Ariyoshi, Koya
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Algorithms; Amino Acid Motifs; Amino Acid Sequence; Amino acids; Antigenic determinants; Antigens; Binding; Biology; Cohort Studies; Computational Biology; Computer Science; Computer simulation; Crystal structure; Crystallography; Cytotoxicity; Docking; Enzyme-linked immunosorbent assay; Epitope mapping; Epitope Mapping - methods; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; Female; gag Gene Products, Human Immunodeficiency Virus - chemistry; gag Gene Products, Human Immunodeficiency Virus - immunology; Genomes; Histocompatibility antigen HLA; HIV; HIV Antigens - chemistry; HIV Antigens - immunology; HIV-1 - chemistry; HIV-1 - immunology; HLA Antigens - chemistry; HLA Antigens - immunology; Human immunodeficiency virus; Humans; Infections; Lymphocytes; Lymphocytes T; Male; Mapping; Mathematical models; Medicine; Molecular Docking Simulation; Peptides; Polymorphism; Predictions; Public health; Simulation; T cell receptors; T cells; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0041703

Class I HLA's polymorphism has hampered CTL epitope mapping with laborious experiments. Objectives are 1) to evaluate the novel in silico model in predicting previously reported epitopes in comparison with existing program, and 2) to apply the model to predict optimal epitopes with HLA using experimental results. We have developed a novel in silico epitope prediction method, based on HLA crystal structure and a peptide docking simulation model, calculating the peptide-HLA binding affinity at four amino acid residues in each terminal. It was applied to predict 52 HIV best-defined CTL epitopes from 15-mer overlapping peptides, and its predictive ability was compared with the HLA binding motif-based program of HLArestrictor. It was then used to predict HIV-1 Gag optimal epitopes from previous ELISpot results. 43/52 (82.7%) epitopes were detected by the novel model, whereas 37 (71.2%) by HLArestrictor. We also found a significant reduction in epitope detection rates for longer epitopes in HLArestrictor (p = 0.027), but not in the novel model. Improved epitope prediction was also found by introducing both models, especially in specificity (p