computational explorations to gain insight into the structural features of tnf-α receptor i inhibitors

Tnf-α is a crucial cytokine in the process of inflammatory diseases. the adverse effect of tnf-α is mostly mediated by interaction of tnf-α with tnf-α receptor type i (tnfr1); therefore, discovery of molecules which can bind to tnfr1 preventing tnf-α-receptor complex formation would be of great interest. in the current study, using grid/golpe program, a 3d-qsar study was conducted on a series of synthetic tnfr1 binders, which resulted in a 3d-qsar model with appropriate power of predictivity in internal (r2 = 0.94 and q2loo = 0.74) and external (r2 = 0.66 and sdep = 0.42) validations. the structural features of tnfr1 inhibitors essential for exerting activity were explored by analyzing the contour maps of the 3d-qsar model showing that steric interactions and hydrogen bonds are responsible for exerting tnfr1 inhibitory activity. to propose potential chemical entities for tnfr1 inhibition, pubchem database was searched and the selected compounds were virtually tested for anti-tnfr1 activity using the generated model, resulting in two potential anti-tnfr1 compounds. finally, the possible interactions of the compounds with tnfr1 were investigated using docking studies. the findings in the current work can pave the way for designing more potent anti-tnfr1 inhibitors.