Drug repurposing combined with MM/PBSA based validation strategies towards MEK inhibitors screening.

Emergence of oncogenic mutations in the MAPK pathway gaining more impact in the recent years. Importantly, MEK is a core element of this pathway as it is easy to inhibit and is a gatekeeper of multiple malignancies. Therefore, we performed strategy to screen repurposed candidate for MEK protein using a library of 11,808 compounds from different clusters in the DrugBank database. Glide docking, Prime-MM/GBSA and QikProp analysis were implemented to retrieve the hits with high precision. The stability of the binding mode and binding affinity of the resultant hit were explored using molecular dynamic simulations and MM/PBSA approach. The results highlight that Nebivolol (DB04861) not only achieved a stable conformation in the MEK binding pocket but also displayed highest binding affinity than the other molecules investigated in our study. Taken together, we hypothesized that Nebivolol is an excellent candidate for the inhibition of MEK in NSCLC patients in future.Communicated by Ramaswamy H. Sarma.