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Online Journal of Bioinformatics ©
Volume 12(2):304-322, 2011
Computational analysis of K-Hefutoxin interaction with Kv channels
and L-carnitine molecule for scorpion envenomation
Amineni Umamaheswari (PhD) 1*, Dibyabhaba Pradhan (M.Sc.) 1, Vani Priyadarshini (M.Sc.)1, Manne Munikumar (M.Sc.)1, PVLN Srinivasa Rao (M.D.)2
1SVIMS Bioinformatics Centre, 2Department of Biochemistry SVIMS University, Tirupati, India
Umamaheswari A, Pradhan D, Priyadarshini V, Munikumar M, Rao S., Computational analysis of K-Hefutoxin interaction with Kv channels and L-carnitine for molecule against scorpion envenomation, Online J Bioinformatics, 12(2):304-322, 2011. Patients who have developed severe heart complications with scorpion envenomation were treated with L-carnitine in SVIMS hospital, Tirupati. Results obtained were encouraging without any side effects. K-hefutoxin blocks Kv1.2 and Kv1.3 currents and also slows the activation kinetics of Kv1.3. In the present study tertiary structure of pore loop regions with voltage sensing domain of Kv channels were built in Modeller 9v7 to study the interaction mode of k-hefutoxin with Kv channels (Kv1.2 and Kv1.3) with L-carnitine. Hex5.1 was used to explore the sites for protein-protein interactions and binding affinities of Kv channels (Kv1.2 and Kv1.3) - k-hefutoxin complexes. The docking results revealed that the active participation of k-hefutoxin functional diad (Tyr5 and Lys19) in blocking Kv channels ion conduction by forming hydrogen bond. Glide 5.5 docking procedure was used to analyze the interaction mode of k-hefutoxin and L-carnitine. The functional diad and disulphide bridge of k-hefutoxin was observed to be disturbed directly by forming intermolecular hydrogen bonds with L-carnitine. Potential of L-carnitine to block the k-hefutoxin Kv channel binding residues is the reason for being a successful drug against scorpion sting. Further, a computer aided virtual screening protocol was followed using Glide 5.5 to explore potential lead molecules from Ligandinfo database. Thirteen lead molecules with higher binding affinity compared to Lcarnitine with good pharmacological properties were identified; those could be considered for designing effective drugs for scorpion envenomation.
Keywords: L-carnitine, potassium channel, scorpion toxin, homology modeling, protein-protein docking, virtual screening