Multi-Pharmacophore Modeling of Caspase-3 Inhibitors using Crystal, Dock and Flexible Conformation Schemes.

Multi-Pharmacophore Modeling of Caspase-3 Inhibitors using Crystal, Dock and Flexible Conformation Schemes. Comb Chem High Throughput Screen. 2018 Jan 01;: Authors: Kumar SP, Jha PC Abstract Numerous caspase-3 drug discovery projects were found to have relied on single receptor as the template to recognize most promising small molecule candidates using docking approach. Alternatively, some researchers were contingent upon ligand-based alignment to build up an empirical relationship between ligand functional groups and caspase-3 inhibitory activity quantitatively. To connect both caspase-3 receptor details and its inhibitors chemical functionalities, we developed multi-pharmacophore model based on flexible (conformations unrestricted or flexible during pharmacophore mapping), dock (conformations obtained using FlexX docking method) and crystal (extracted from multiple caspase-3-ligand complexes from PDB repository) conformations of query ligands. We noticed better sensitivity with good specificity measures returned by candidate pharmacophore hypotheses across each conformation type and recognized crucial pharmacophore features that enable caspase-3 binding. The hit list of the five candidate pharmacophore hypotheses in the multi-pharmacophore model was combined to identify the most common molecules demonstrated using ZINC database search. We believe that better caspase-3 inhibitors can be recognized efficiently by adapting multi-pharm...
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research