Docking of this compound into the active site of chymase cle

Docking of this compound into the active site of chymase clearly demonstrated that the three HBA, two HY_AR, and one HY_AL features of LB_Model have engendered numerous imperative interactions with key amino acids such as Lys40, His57, Lys192, Quisinostat cost Gly193, and Ser195. Thus, presence of chemical features essential to interact with key active site residues and discriminative power of developed models to active chymase inhibitors implicated that multiple pharmacophore- based virtual screening may provide an efficient approach to find novel chymase inhibitors from available databases. Third method to validate the generated ligand and structurebased pharmacophore models is the scale fit value method. The main purpose of this validation method is to verify the ability of pharmacophore models to distinguish between experimentally known chymase inhibitors based on their activity values. A set of 20 chymase inhibitors with diverse range of activity TY-52156 values from 1 nM to 1800 nM was selected and mapped over generated pharmacophore models. Results of this pharmacophore mapping over chymase inhibitors returned various fit values. A meticulous analysis of these fit values revealed that there was a good correlation between experimentally known activity values and fit values generated by pharmacophore mapping. Thus, the result of this validation technique clearly indicates that the selected ligand and structure-based pharmacophore models have the capability to single out most active inhibitors form less active chymase inhibitors. To further validate representative pharmacophore models and demonstrate their efficiency, SB_Model1, SB_Model2, SB_ Model4, and LB_Model were used as 3D queries to screen the chemical databases like Maybridge and Chembridge which consist of 59 652 and 50 000 compounds, respectively. Prior to multiple pharmacophore-based virtual screening experiments, both databases were transformed to druglike databases by Prepare Ligands and ADMET Descriptors protocols of DS. After preparation of druglike databases, all four pharmacophore models were subjected to screening of these druglike databases. For SB_Model4 which holds six features, Maximum omitted feature was set to 1 and for all other three models it was set to 0. The retrieved database hits were then ranked