Computational design and analysis of a lung cancer vaccine targeting EGFR mutation E709G

Non-small cell lung cancer remains a leading cause of cancer-related mortality, driven significantly by specific EGFR mutations. This study utilized a quantum-inspired immunoinformatics framework to design a novel, self-adjuvanted multi-epitope vaccine specifically targeting the atypical EGFR E709G mutation. The computational methodology integrated a β-defensin adjuvant with HLA-I and HLA-II specific epitopes via optimized linkers to ensure simultaneous innate and adaptive immune engagement. Quantitative computational evaluations revealed strong predictive antigenicity (VaxiJen score = 0.8676) without inducing toxicity or allergenicity. Molecular docking simulations demonstrated highly favorable binding affinities to critical immune receptors, notably predicting robust interactions with HLA-I (HLA-A*11:01) and HLA-II (HLA-DRB1*15:01) molecules to effectively stimulate CD8+ and CD4+ T cells. To definitively validate the long-term dynamic stability and conformational reliability of the predicted complexes, extended molecular dynamics (MD) simulations were performed over a 100 ns trajectory. The rigorous computational trajectories confirmed highly stable bindings, consistent hydrogen bond networks, and favorable interaction energies within the functional grooves of both HLA-I and HLA-II receptors without disrupting the native protein folding. Furthermore, quantum-based physicochemical analyses confirmed optimal thermodynamic stability, high surface reactivity (TPSA = 2249.60 Å 2 ), and excellent solubility (LogP = − 26.02). In silico cloning into a pET-28a( +) expression vector, supported by strategic codon optimization (GC content increased to 58.65%), indicated a highly favorable profile for functional bacterial expression. These quantitative in silico findings successfully establish a high-fidelity structural template, suggesting that the designed vaccine construct possesses substantial immunotherapeutic potential and warrants further in vitro and in vivo experimental validation.