Peptídeos da peçonha de escorpiões e sua interação com Nav1.7: revisão bibliográfica e modelagem molecular.

Abstract

Scorpions from the Buthidae family produce a wide range of neuroactive peptides capable of modulating ion channels, especially voltage-gated sodium channels (Nav). These peptides are increasingly of interest in biomedical research due to their therapeutic potential for disorders involving neuronal excitability. In this study, five bioactive peptides from different scorpion genera were selected and evaluated for their ability to interact with the Nav1.7 sodium channel, a key target in conditions like neuropathic pain. Sequences were obtained from the UniProt database and used for structural modeling with AlphaFold, followed by stereochemical validation using PROCHECK. All peptides produced high-quality three-dimensional models, with over 90% of residues in favorable regions of the Ramachandran plot. Molecular docking with HADDOCK was then performed to assess affinity, stability, and structural compatibility. Beta-toxin Cn4, MeuNaTxalpha-1, and AaH II showed the best docking results, with lower HADDOCK scores and more consistent interactions, indicating strong modulatory potential. Conversely, Bom IV and Delta-butx-hj2a exhibited fewer stable interactions, as reflected by higher RMSD values. Overall, the findings demonstrate that in silico methods are valuable tools for initial screening of bioactive peptides and provide useful insights for future experimental research and the identification of promising candidates for therapeutic development.