Interaction of DisBa01 peptide from Bothrops alternatus venom with BRAF melanoma receptors: Modeling and molecular docking

Abstract

Metastatic melanoma is highly aggressive and challenging, often leading to a grim prognosis. Its progression is swift, especially when mutations like BRAFV600E continuously activate pathways vital for cell growth and survival. Although several treatments target this mutation, resistance typically emerges over time. In recent decades, research has underscored the potential of snake venoms and peptides as bioactive substances for innovative drugs, including anti-coagulants, anti-microbial, and anti-cancer agents. Leveraging this knowledge, we propose employing a bioinformatics simulation approach to: a) Predict how well a peptide (DisBa01) from Bothrops alternatus snake venom binds to the melanoma receptor BRAFV600E via Molecular Docking. b) Identify the specific peptide binding sites on receptors and analyze their proximity to active receptor sites. c) Evaluate the behavior of resulting complexes through molecular dynamics simulations. d) Assess whether this peptide qualifies as a candidate for anti-melanoma therapy. Our findings reveal that DisBa01 enhances stability in the BRAFV600E melanoma receptor structure by binding to its RGD motif, an interaction absent in the BRAF WT model. Consequently, both docking and molecular dynamics simulations suggest that DisBa01 shows promise as a BRAFV600E inhibitor.