3.2 | A small molecule compound targeting UHRF1 protein
was identified using molecule docking approach.
UHRF1 has become a potential drug target for PCa, which inspired us to
search for small molecule inhibitors targeting UHRF1 protein. From the
most commonly used 36 traditional Chinese medicines for the treatment of
PCa in China (wanli&hong, 2018), we screened 75 small molecule
compounds using TCMSP database, and then performed molecular docking
with the five crystal structure domains of UHRF1 that were obtained from
the PDB database. The heatmap shows the binding energy of
the docking of 75 small molecules on 5 domains of UHRF1 by using
autodock vina. After performing the hierarchical clustering analysis
using the pheatmap R package (Fig. 2a). Among them, DSG and Luteolin
7-glucoside (L7G) have the best comprehensive scores. L7G is a flavonoid
compound (Fig. 2b), DSG is a steroidal saponin (Fig. 2c). To clarify how
small molecule compounds L7G and DSG interact with UHRF1 protein, we
re-analyzed the molecular docking results, and predicted the most
binding possibility of small molecules with protein domains. The results
demonstrate that L7G binds the UBL domain of UHRF1 (Fig. 2d-f), while
DSG binds the TTD domain of UHRF1 (Fig. 2e-g). We focused on L7G and DSG
for further studies in the subsequent experiments.