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.