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Online Journal of Bioinformatics ©
Volume 11 (1):103-124, 2009
Phylogenetic analysis, homology modeling, molecular dynamics, docking and structure based designing of new inhibitors against cinnamyl alcohol dehydrogenase (CAD) cloned and sequenced
from a leguminous tree subabul (Leucaena leucocephala)
Sekhar NP1, Kumar RD2, Sirisha VL2, Prashant S2, Kavi Kishor PB1
Sekhar NP, Kumar RD, Sirisha VL, Prashant S, Kavi Kishor PB, Phylogenetic analysis, homology modeling, molecular dynamics, docking and structure based designing of new inhibitors against cinnamyl alcohol dehydrogenase (CAD) cloned and sequenced from a leguminous tree subabul (Leucaena leucocephala), Onl J Bioinform., 11 (1):103-124, 2009. Cinnamyl-alcohol dehydrogenase (CAD; EC 188.8.131.52) catalyzes the final step in the branch of phenylpropanoid synthesis specific for production of lignin monomers. The homology model of CAD enzyme cloned and sequenced by us from subhabul was build by energy minimization and molecular dynamics in a solvated water layer. The refined protein showed that the enzyme have 11 a-helices and 20 β-sheets with a catalytic and nucleotide binding domains forming a rossmanfold. Superimposition of the refined model with the template showed 1.38Å. Structural analysis of CAD with the templates revealed highly conserved GHE pattern. Docking studies show that NADPH acts a cofactor for the enzyme CAD from subhabul. In the presence of co-factor, 5-hydroxy coniferyl aldehyde binds with high affinity with the enzyme predicting to be the major substrate for the enzyme CAD. Pharmacophore based docking of 5-hydroxy coniferyl aldehyde show that 5-(2-hydroxyethyl)-6-methyl-pyrimidine-2, 4-diol inhibitor binds with high affinity compared to the natural substrates. Docking studies also shows that His48, Ser49 and His52 plays an important role in binding of the substrates, products and inhibitors.
Keywords: Cinamyl alcohol dehydrogenase, homology modeling, docking