Using Pharmacophore and Docking Models to Gain Insight into Structural Binding and Virtual Screening: An Application Study with c-Src Kinase

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, Ph armacophore m odds were g enerated based upon a series of 29 structurally diverse chemicals exhibiting IC (50) 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 scree fling experiments, we retrieved 60 compounds, which are having best mapping with the pharmacophore model, from an in-house database containing 500 000. When these compounds were docked, 28 compounds are having good interaction with c-Src kinase, especially with the hinge region amino acid