In-Silico Identification of Bee Venom Peptides (Melittin and Tertiapin) as Potential Anti-Angiogenic Agents Targeting Tumor-Associated Receptors

Abstract

Tumor angiogenesis plays a critical role in cancer growth and metastatic progression and therefore represents an important therapeutic target. Bee venom-derived peptides constitute a diverse source of bioactive molecules whose interactions with angiogenesis-associated receptors remain incompletely characterized. In this study, an integrated in silico workflow was applied to investigate the potential interactions of selected bee venom peptides, including melittin and tertiapin, with major angiogenic-associated receptors, including platelet-derived growth factor receptor alpha (PDGFR-α), vascular endothelial growth factor receptors, fibroblast growth factor receptors, and integrin αvβ3. Molecular docking was used to identify and prioritize potential peptide–receptor complexes, while molecular dynamics simulations were performed to assess their conformational stability and interaction patterns under the simulated conditions. Reactome pathway enrichment analysis was subsequently used to contextualize the selected molecular targets within angiogenesis-related biological processes. Melittin–PDGFR-α and tertiapin–integrin αvβ3 emerged as the highest-ranked complexes and exhibited relatively stable interaction patterns with persistent intermolecular contacts throughout the simulations. Pathway enrichment analysis further associated the investigated targets with PDGFR signaling, cell migration, and other angiogenesis-related processes. Collectively, these findings suggest that melittin–PDGFR-α and tertiapin–integrin αvβ3 represent promising peptide–receptor pairs for further investigation while providing a computational rational for exploring bee venom peptides as potential modulators of tumor angiogenesis. However, these findings should be considered hypothesis-generating and primarily serve to prioritize peptide-receptor pairs for future experimental validation, including binding assays, cellular assays, and relevant in vivo studies. Peptide selectivity, toxicity, stability, and targeted delivery should also be evaluated before any therapeutic application can be considered.