The protein – ligand interactions were examined by DS. Hit molecules which showed the expected interactions with the critical amino acids present in the active site of the protein, and comparable high binding scores than the bound ligand, were selected as potent inhibitors of chymase. Synthetic accessibility scores for all four hit JNJ-63533054 compounds were used to validate the synthetic possibilities. SYLVIA v 1.0 program from the Molecular Networks group was employed to calculate the synthetic accessibility of these optimized compounds. The estimation of synthetic accessibility using SYLVIA provides a number between 1 and 10 for compounds that are very easy to synthesize and compounds that are very difficult to synthesize, respectively. The method for calculating synthetic accessibility takes account of a variety of criteria such as complexity of the molecular structure, complexity of the ring system, number of stereo centers, similarity to commercially available compounds, and DCVC potential for using powerful synthetic reactions. These criteria have been individually weighted to provide a single value for synthetic accessibility. In the present study, we carried out a DFT-based quantitative structure�Cactivity relationship study for both experimentally known chymase inhibitors and final hits. To obtain a significant correlation, it is fundamental that apposite descriptors be employed, whether they are theoretical, empirical, or experimental features of the structures. DFT is today one of the best methods to study medium size and larger molecular systems. The best DFT methods achieve substantially greater precision than the Hartree�CFock theory at only a modest augment in cost. They accomplish this task by incorporating few effects of electron correlation much less affluently than traditional correlated methods. A range of functional has been defined, generally distinguished by the manner that they treat the exchange and correlation components. The best known of the hybrid functionals is Becke��s three-parameter formulation B3LYP. Complete geometry optimization for data set compounds was carried out using DFT with B3LYP, using basis set 6-31G* level. A useful kind of net atomic charges, called electrostatic potential -fitting charges, were derived from the DFT calculated
