Abstract:Epitope mapping has emerged as a powerful tool to develop peptide vaccines against hypervariable viruses such as HIV. This method has led to stimulate a specific immune response and achieve advanced vaccine formulations. In this study, we identified peptides that were potentially immunostimulatory and highly conserved in HIV‐1 main group. The analyses included were CTL assay, Tap transport, and the potential allergenicity. The highest population coverage rate was also found for all potential T‐cell epitopes in 16 specified geographic regions of the world. The current study is the first attempt to explore peptide‐protein flexible docking across all the major epitopes of HIV‐1. Our data indicated that REV54‐63and VPU58‐66 with the highest epitope identification scores, GP16037‐46 and VPR38‐47 with the highest conservation (98.89%), and NEF134‐144 and GP16037‐46 epitopes with a higher quality of peptide‐protein interaction models in docking procedure were chosen as putative epitopes among all HLA class I epitopes. TAT40‐67, VPR65‐82, and VPU30‐44 with the highest score of binding affinity, VPR65‐82 with the highest conservation (97.55%), and GP160481‐498 epitope with a higher quality of peptide‐protein interaction models in docking procedure were determined as putative epitopes among all HLA‐DR epitopes. Furthermore, two epitopes of GP160481‐498 and VIF144‐159 were predicted to bind 22 and 21 HLA‐II alleles, respectively. Accumulative population coverage of potential helper T‐cell epitopes and CTL epitopes varied between 90.82% and 100%. Generally, these predicted highly immunogenic T‐cell epitopes can contribute to design HIV‐1 peptide vaccine candidates. Combination of bioinformatics tools with in vivo methods will be necessary for HIV‐1 vaccine development.