Coarse-grained molecular dynamics-guided immunoinformatics to explain the binder and non-binder classification of Cytotoxic T-cell epitope for SARS-CoV-2 peptide-based vaccine discovery

• DOI: 10.1371/journal.pone.0292156
• Publication Date: 2023-10-05T17:47:48Z
• Authors: Muhammad Yusuf; Wanda Destiarani; Wahyu Widayat; Yosua Yosua; Gilang Gumilar; Angelica Shalfani...; Fauzian Giansyah ...; Farhan Azhwin Mau...; Umi Baroroh; Ari Hardianto; Rani Maharani; Neni Nurainy; Acep Riza Wijayad...; Ryan B. Ristandi; Ines Irene Cateri...; Toto Subroto
• Keywords: COVID-19 Vaccines; HLA-A Antigens; SARS-CoV-2; Science; Q; R; Epitopes, T-Lymphocyte; COVID-19; Antineoplastic Agents; Molecular Dynamics Simulation; 3. Good health; Molecular Docking Simulation; Vaccines, Subunit; Medicine; Humans; Epitopes, B-Lymphocyte; Peptides; Research Article

Epitope-based peptide vaccine can elicit T-cell immunity against SARS-CoV-2 to clear the infection. However, finding the best epitope from the whole antigen is challenging. A peptide screening using immunoinformatics usually starts from MHC-binding peptide, immunogenicity, cross-reactivity with the human proteome, to toxicity analysis. This pipeline classified the peptides into three categories, i.e., strong-, weak-, and non-binder, without incorporating the structural aspect. For this reason, the molecular detail that discriminates the binders from non-binder is interesting to be investigated. In this study, five CTL epitopes against HLA-A*02:01 were identified from the coarse-grained molecular dynamics-guided immunoinformatics screening. The strong binder showed distinctive activities from the non-binder in terms of structural and energetic properties. Furthermore, the second residue from the nonameric peptide was most important in the interaction with HLA-A*02:01. By understanding the nature of MHC-peptide interaction, we hoped to improve the chance of finding the best epitope for a peptide vaccine candidate.