Abstract
The α-conotoxins are neurotoxic peptides produced during predation and defense mechanisms of Conus organisms. Previous studies focused on their binding with nicotinic acetylcholine receptors (nAChRs) only as binding with other neuroreceptors such as voltage-gated sodium channels were not observed. In this study, a computational approach was used to bind 19 α-conotoxins from the A superfamily on a bacterial voltage-gated sodium channel (NavMs) receptor from the Magnetococcus sp. (strain MC-1). Preparation was performed using PyMOL, and the ligand-receptor interactions were simulated using DINC 2.0, an incremental docking approach based on genetic algorithm. Based on the binding energies (in kcal/mol), the reaction between the voltage-gated sodium channel and α-conotoxins is both a favorable spontaneous process thermodynamically and characteristic to the pharmacological class due to highly negative and close range of values. Additionally, RMSD values provided further insights on different channel conformations after molecular docking studies. Lastly, conotoxin BuIA (PDB ID 2I28) with a binding energy of −6.87 \(\pm\) 0.2357 kcal/mol is the most probable active conotoxin. Findings of this study are significant for α-conotoxins as potential novel drugs for voltage-gated sodium channels which are commonly involved in neurological diseases.
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Acknowledgements
The authors wish to express their most heartfelt gratitude to Dr. Lemmuel L. Tayo for the guidance and expertise on conotoxins throughout this study.
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Tayo, L.L., Aquino, A.C., Pasamba, E.C. (2023). Molecular Docking Studies on the Binding Affinity of Alpha-Conotoxins on Voltage-Gated Sodium Ion Channel Using an Incremental Genetic Algorithm Approach. In: Chen, SM. (eds) Proceedings of 10th International Conference on Chemical Science and Engineering. ICCSE 2021. Springer Proceedings in Materials, vol 21. Springer, Singapore. https://doi.org/10.1007/978-981-19-4290-7_10
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DOI: https://doi.org/10.1007/978-981-19-4290-7_10
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