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DOI: 10.7763/IJESD.2010.V1.9
Using Pharmacophore and Docking Models to Gain Insight into Structural Binding and Virtual Screening: An Application Study with c-Src Kinase
Abstract—c-Src kinase is a non receptor tyrosine kinase that acts as a signal transduction inhibitor, useful to treat various diseases, including cancer, osteoporosis, and metastatic bone disease. To discover novel high affinity ligands, Pharmacophore models were generated based upon a series of 29 structurally diverse chemicals exhibiting IC50 values from 2.7nM to 50 000nM for this protein. The model was validated by using 263 compounds as test set, which has a correlation coefficient of 0.750 between estimated activity and experimentally measured activity. For analyzing intermolecular interactions between protein and ligand, all the molecules were docked. Docking analysis suggests the role of hydrogen bonding in enzyme selectivity. In virtual screening experiments, we retrieved 60 compounds, which are having best mapping with the pharmacophore model, from an inhouse database containing 500000 compounds. When these compounds were docked, 28 compounds are having good interaction with c-Src kinase, especially with the hinge region amino acids.
Index Terms—Pharmacophore, Docking, c-Src, Virtual Screening
bioCampus, GVK Biosciences, S-1, Phase-1, Technocrats Industrial Estate, Balanagar, Hyderabad 500 037, Andhra Pradesh, India
Bioinformatics Division, Environmental Microbiology Lab, Department of Botany, Osmania University, Hyderabad 500007, Andhra Pradesh, India
Ravambio, Begumpet, Hyderabad 500016, Andhra Pradesh, India.,
National Institute of Pharmacutical Education and Research, Hyderabad ,500 607, Andhra Pradesh, India.
Acharya Nagarjuna University, P. G center, Nuzvid, 521201, Andhra Pradesh, India.
Corresponding author e-mail:kranthigvk@gmail.com, Mobile:9676955664
Cite: Kranthi Raj K, Rekha R, Lokesh. P, Muttineni Ravikumar, D. Ramachandran, "Using Pharmacophore and Docking Models to Gain Insight into Structural Binding and Virtual Screening: An Application Study with c-Src Kinase," International Journal of Environmental Science and Development vol. 1, no. 1, pp. 40-46, 2010.
