In-silico Evaluation of Spider Venom Peptide Lycosin-I for Triple Negative Breast Cancer Immunotherapy

Objectives: This study aims to evaluate spider venom-derived peptide Lycosin-I, as a potential PD-I pathway inhibitor to immunotherapeutically treat triple-negative breast cancer (TNBC) in combined in silico approach. Methods: The protein validation accuracy was assessed by using SWISS-MODEL, Verify 3D, ProSA-web, and MolProbity. Various tools in bioinformatics were used to determine the physiochemical peptide profiling including toxicity, allergenicity, antigenicity, and hemolytic potential, as well as the cell-penetrating activity. Molecular docking using ClusPro 2.0 and 100 ns molecular dynamics (MD) simulation were used to evaluate the interaction and stability of the complex between Lycosin-I and PD-I. Results: Lycosin-I exhibited favorable safety profile characterized by non-toxicity, non-allergenicity, non-antigenicity, and relatively low hemolytic potential. Docking analysis revealed strong binding affinity with lowest weighted score of -697.4 between PD-I and Lycosin-I, while Molecular dynamics (MD) simulations confirmed structural stability with a slight fluctuation of the RMSD (~1.530A post-equilibration), showing that Lycosin-I significantly modulates the PD-I/PD-LI axis, suggesting its role as a potent immunoregulatory agent. Conclusion: In-Silico results showed that Lycosin-I establishes itself into a strong binding interaction with PD-I, which prevents PD-LI binding, which indicates its possibilities as a new immunotherapeutic candidate.