title: 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.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Bioinformatics, Sathyabama University, Chennai, Tamil Nadu, India.
authors.forename: R Barani
authors.initials: RB
authors.lastname: Kumar
authors.affiliation: Department of Bioinformatics, Sathyabama University, Chennai, Tamil Nadu, India.
authors.forename: B Shanmuga
authors.initials: BS
authors.lastname: Priya
authors.affiliation: Department of Bioinformatics, Sathyabama University, Chennai, Tamil Nadu, India.
authors.forename: M Xavier
authors.initials: MX
authors.lastname: Suresh
mesh_terms: D000818:Animals; D000992:Antitoxins / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain; D018999:Charybdotoxin / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D003198:Computer Simulation; D015195:Drug Design; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D026902:Potassium Channel Blockers / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011487:Protein Conformation; D012605:Scorpions / Q000737:chemistry
chemical_list: D000992:Antitoxins; D008024:Ligands; D026902:Potassium Channel Blockers; D018999:Charybdotoxin
keywords: Antidote; homology modeling; inhibitors; ion channel blockers; neurotoxin