Homology Modeling of Mus Musculus CDK5 and Molecular Docking Studies with Flavonoids

Seshagiri Bandi; Sowmya Suri; Rumana Waseem; Sania Shaik

Seshagiri Bandi Bioinformatics Division, Osmania University, Hyderabad – 500007
Sowmya Suri Bioinformatics Division, Osmania University, Hyderabad – 500007
Rumana Waseem Bioinformatics Division, Osmania University, Hyderabad – 500007
Sania Shaik Bioinformatics Division, Osmania University, Hyderabad – 500007

Keywords: CDK-5, Flavonoids, Molecular modeling, Modeller9.17, Autodock4.2.

Abstract

A 3D model of Cyclin-dependent kinase 5 (CDK5) (Accession Number: Q543f6) is generated based on crystal structure of P. falciparum PFPK5-indirubin-5-sulphonate ligand complex (PDB ID: 1V0O) at 2.30 Å resolution was used as template. Protein-ligand interaction studies were performed with flavonoids to explore structural features and binding mechanism of flavonoids as CDK5 (Cyclin-dependent kinase 5) inhibitors. The modelled structure was selected on the basis of least modeler objective function. The model was validated by PROCHECK. The predicted 3D model is reliable with 93.0% of amino acid residues in core region of the Ramachandran plot. Molecular docking studies with flavonoids viz., Diosmetin, Eriodictyol, Fortuneletin, Apigenin, Ayanin, Baicalein, Chrysoeriol and Chrysosplenol-D with modelled protein indicate that Diosmetin is the best inhibitor containing docking score of -8.23 kcal/mol. Cys83, Lys89, Asp84. The compound Diosmetin shows interactions with Cys83, Lys89, and Asp84.