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OJBTM
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
ABSTRACT
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