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Virtual inhibitors of L-Type
calcium channel
Madhu Sudhana Saddala
and A. Usha Rani*
Department of Zoology, DBT-Bioinformatics
center, Sri Venkateswara
University, Tirupati –
517502, A.P., India.
ABSTRACT
Saddala
MS, Rani U., Virtual inhibitors of L-Type calcium channel, Onl
J Bioinform.,
14(2):213-225,
2013.
Cadmium (Cd) is a toxic
metal. Diet, occupation and smoking are the primary routes of
exposure in
humans which can results in a variety of adverse effects. Cd
may allow the
entry of excess calcium through voltage-dependent
L- type calcium channel (VLCC) which regulates smooth
and cardiac muscle
contraction. Therefore VLCC could be a potential drug target.
Diltiazem (CID 39186)
is a vasodilator due to its
antagonistic
activity on calcium ions on membrane receptors and is a
potential
blocker of the target protein. VCLC was
energy minimized and subjected to molecular dynamic
simulations using NAMD 2.9
software with CHARMM27 force field in water The receptor
structure was
minimized 25,000 steps for 500 ps
and simulated 1,000,000
steps for 2ns. 4500 compounds were screened from PubChem
database through structure based virtual screening with
reference to Diltiazem. The
screened compounds were docked into the
active site of the protein using Autodock
Vina in PyRx
Virtual Screening
tool. The
docking results shows that the compounds CID08830211, CID13650942,
CID65739916 and CID65748951
had -9.0, -8.6, -8.4 and -8.2kcal/mol
respectively.
Through the interaction analysis, it
was found that
Asp, Thr, Leu,
Arg, Tyr, Gln,
Pro, Glu, Phe,
and His residues of
3LV3 protein were important anchoring residues for the
ligands which are main
contributors to the blockers interactions.
Keywords: Docking, Diltiazem,
H-bond, CCBs, 3LV3,
Autodock Vina