In silico analysis of potential inhibitors of Ca(2+) activated K(+) channel blocker, Charybdotoxin-C from Leiurus quinquestriatus hebraeus through molecular docking and dynamics studies.

Objective: Charybdotoxin-C (ChTx-C), from the scorpion Leiurus, quinquestriatus hebraeus blocks the calcium-activated potassium channels and causes hyper excitability of the nervous system. Detailed understanding the structure of ChTx-C, conformational stability, and intermolecular interactions are required to select the potential inhibitors of the toxin.

Materials And Methods: The structure of ChTx-C was modeled using Modeller 9v7. The amino acid residues lining the binding site were predicted and used for toxin-ligand docking studies, further, selected toxin-inhibitor complexes were studied using molecular dynamics (MD) simulations.

Results: The predicted structure has 91.7% of amino acids in the core and allowed regions of Ramachandran plot. A total of 133 analog compounds of existing drugs for scorpion bites were used for docking. As a result of docking, a list of compounds was shown good inhibiting properties with target protein. By analyzing the interactions, Ser 15, Lys 32 had significant interactions with selected ligand molecules and Val5, which may have hydrophobic interaction with the cyclic group of the ligand. MD simulation studies revealed that the conformation and intermolecular interactions of all selected toxin-inhibitor complexes were stable.

Conclusion: The interactions of the ligand and active site amino acids were found out for the best-docked poses in turn helpful in designing potential antitoxins which may further be exploited in toxin based therapies.