A computational perception of BBOX1-IP3R3 interaction uncovers inhibitors for dysregulated calcium signalling in triple negative breast cancer.

Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer unveiling negative expression on oestrogen receptors, progesterone receptors, and HER2. The anomalous activation of signalling pathways and specific types of mutations characterize the progression of TNBC. Protein-protein interaction in the tumour microenvironment plays a crucial role in tumour aggressiveness. Disrupting the signalling pathways that promote cell progression, migration, and survival opens up a promising avenue for targeting the aggressive form of TNBC. The present study emphasizes the molecular interaction mechanism driving the aggressive and recalcitrant TNBC between BBOX1-IP3R3. The BBOX1-IP3R3 complex destabilization was accomplished using compounds obtained from various databases through virtual screening, molecular, and essential dynamics. The interaction study revealed that the four hits bound at the interface and facilitated better binding affinity with the highest docking score and optimal binding free energy. In addition, the molecular dynamics simulation, PCA/FEL, and MM/PBSA analysis conclusively evaluate the binding potential of the compounds and unequivocally stabilize specific conformations or deception of the complexes in high-energy states. Thus, the identified compounds lead to the disruption of BBOX1-IP3R3 interaction, which aids in the therapeutic option of TNBC.