Homology modelling and docking study of SUZ12, a subunit of PRC2 complex, with naturally occurring plant compounds

Abstract

PRC2 is a transcriptional repressive complex and its inhibitors have been found to have a potential role in cancer therapeutics. In this study, SUZ12-a subunit of PRC2 complex was studied with the help of protein-ligand docking for various naturally occurring plant steroids and flavonoids. The structure of SUZ12 was modeled by homology modeling tool and validated with the help of various computational tools. The best model was selected based on the percentage of residues that are present in either of favored, allowed or disallowed regions using the Ramachandran Plot. This was further followed by docking studies with plant-based flavonoids and phytosterols (Tangeritin, Apigenin, Diosgenin, Luteolin, and Guggulsterone) using Patchdock and YASARA docking software. Luteolin and Guggultserone were observed to have the highest binding energies towards SUZ12 and Tageratin scored the lowest. Luteolin, Guggulsterone, and apigenin showed binding at the zinc finger domain. Thus, this virtual screening for binding of various compounds identified that luteolin and apigenin might disrupt the secondary structure of SUZ12 protein and thus hamper the functioning of PRC2. This analysis can be further used for the designing of potent drugs against diseases caused by hyperactivation of the PRC2 complex, thereby aiding knowledge in the field of research. © 2020, Advanced Scientific Research. All rights reserved.