Docking Study of Ligands Targeting NLRP3 Inflammatory Pathway for Endodontic Diseases

The NLRP3 (NOD-like receptor family containing a pyrin domain 3) inflammasome pathway has a crucial role in the dental immune system and is associated with the activation of the dental immune response. Therefore, it is a specific target for drug molecules to be selected in the treatment of endodontic diseases. Various NLRP3 inflammatory and caspase-1 inhibitors that exhibit effective inhibition against inflammatory conditions have been identified in previous studies. In this study, the human NLRP3 model was constructed by the loop modeling method using computer-aided programs. Binding affinities, inhibition constants (Ki), and ligand-protein interactions of the selected ligands were calculated and investigated by molecular docking simulation against the inflammasome NLRP3 and caspase-1. Binding modes and calculations were performed according to Lamarckian genetic algorithm. The calculated docking scores for each ligand used in this study were between the range of -5.1 and -11.8 kcal/mol for the inhibitory activity. CY-09 (a NLRP3 inflammasome inhibitor) and VX-765 (a caspase-1 inhibitor) were shown to have the most desirable binding affinities, Ki values, and strong binding interactions in the NLRP3 and human caspase-1 binding pockets, respectively. The combination of CY-09 and VX-765 ligands can be used to prevent inflammation in the treatment of endodontic diseases. These inhibitors could be used in the future treatment of endodontic infections and to improve the viability of root canal drugs and pulp capping materials.