The two HY groups were pointed towards Phe191 and Gly216, an

The two HY groups were pointed towards Phe191 and Gly216, and HBD pointed towards Tyr215. While, the RA feature was directed towards His57 and two NI features were pointed in the direction of Lys192 and Gly193. The comparison of above four pharmacophore models showed that hydrophobic feature was the common feature among all developed pharmacophore models. A previous study also showed that presence of hydrophobic sites for a chymase inhibitor were important for its buy 801312-28-7 effective binding with the key Olaparib residues of the active site. Pharmacophoric features of the models were directed towards key amino acids like Tyr215, His57, Lys192, Gly193, and Ser195 which play a major role in chymase inhibition activity. Hence, these features can be considered as important chemical features to discover the novel chymase inhibitors. Common feature pharmacophore models were generated for the target protein using set of experimentally known inhibitors. With the aim of acquiring a best model, numerous common feature pharmacophore generation runs were performed by altering the parameters such as minimum interfeature distance values, maximum omit feature, and the permutation of pharmacophoric features. The qualitative top ten pharmacophore models were developed using Common Feature Pharmacophore Generation/DS to identify the common features necessary to inhibit chymase. Direct and partial hit mask value of 1�� and 0�� for models connoted that the molecules present in dataset were well mapped to all the chemical features in the models and there is no partial mapping or missing features. The Cluster analysis was used to evaluate and categorize the difference between the compositions of models�� chemical features and locations. These models could be roughly classified into two clusters according to the pharmacophoric features presented. The first eight models in cluster I identified six functional features, including three HBA, hydrophobic aromatic, hydrophobic aliphatic, and ring aromatic centers. The models in cluster II recognized five functional features, with two HBA, one HY_AL, and two RA. The distances between some pharmacophoric features in all models were rather constant, whereas some distances fluctuated in a relatively br