In Silico screening for potential Developmentally Regulated

Abstract

Developmentally regulated GTP-binding protein 2 (DRG2) is involved in various physiological functions. There are currently no reports on the role of DRG2 in cellular metabolisms. To get insights into the role of DRG2 in metabolism, we analyzed the interactions between DRG2, and 420 metabolites collected from the Human Metabolome Database (HMDB) by computational docking studies. In silico molecular docking analysis identified 37 metabolites showing binding energy with DRG2 higher than GTP (-6.9 kj\mole). Most of them were involved in steroid hormone metabolism. We also determined the amino acid residues of DRG2 involved in the interaction with these metabolites. We demonstrated that some metabolites share amino acid residues of DRG2 for their binding with GTP, suggesting that these metabolites may compete with GTP for binding with DRG2 and thus affect DRG2 activity. BioMuta (a database of cancerassociated single-nucleotide variations) analysis revealed variations within the amino acid residues of DRG2 responsible for binding with these metabolites in human cancer cells. These suggest that DRG2 may interact with hormones and play important roles in the regulation of hormone metabolism and that disruption of these interactions may affect the growth and metastasis of cancer cells.