In-silico identification of potential antagonists for human Casein kinase II subunit alpha' (CK2α2)

Abstract

AbstractHuman CK2α2 is an enzyme that belongs to the Serine/Threonine protein kinase family which is involved in signal transduction. Over expression of CK2α2 causes kidney cancer therefore, human CK2α2 has been identified as a drug target for the development of potential antagonists against cancer therapy. The existing human CK2α2 inhibitors in clinical practice are having side effects like fatigue, diarrhea, nausea, anorexia and vomiting. High-throughput virtual screening is one of the most common method used to identify lead compounds was implemented in the present study to identify potential inhibitors of human CK2α2. The co-crystal structure of human CK2α2 was retrieved from the protein data bank. A 2D similarity search was performed for available five human CK2α2 inhibitors (Apigenin, VX680, Sunitinib, SUI4813 and CCK) taken from PDB and PubMed to acquire 1942 structural analogs. The 3D structural conversion and multiple confirmations for 1942 compounds were generated using LigPrep. The docking and scoring calculations were performed using Glide v5.7 which includes high throughput virtual screening (HTVS), Standard precision (SP) docking and extra precision (XP) docking. Obtained 39 leads were compared with docking scores of the existing inhibitors and proposed six leads having good binding affinity. The binding orientation of CK2α2-lead 1complex was correlating with native co-crystal structure. Hence, lead ‘1’ can be suggested as potent inhibitor against human CK2α2 involved in kidney cancer.