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


Sivakumar Prasanth Kumar* and Prakash C Jha  


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-pharmacophore models.


caspase-3, pharmacophore modeling, conformational space explorations, docking, apoptosis.


School of Chemical Sciences, Central University of Gujarat, Gandhinagar - 382030, Gujarat, School of Chemical Sciences, Central University of Gujarat, Gandhinagar - 382030, Gujarat

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