Screening and Analysis for Inhibitors of SHMT2 Enzyme Protein

Abstract

Abstract Mitochondrial serine hydroxymethyl transferase isoform 2 (SHMT2) plays a crucial role as a catalytic regulator in the serine/glycine pathway of cancer cells' one-carbon metabolism. Although it has potential as an anti-cancer target, only a limited number of inhibitors have been identified. In this study, we used eight different scoring functions and skeleton clustering to screen the ChemDiv database for 22 compounds, most of which have the same skeleton structure. ASIE was used to identify the key residues in SHMT2 and chemical groups in the inhibitors. Through quantitative determination of the binding energy of each residue, important features of the protein-inhibitor interaction were revealed. The most significant contributing residues were TYR105 and TYR106 in the B chain, as well as LEU166 and ARG425 in the A chain. These results could guide the development of more potent inhibitors and enhance our understanding of the drug-SHMT2 binding mechanisms, and it served as a guide for future drug design.