Design and interaction mechanism of ligand targeted with folate receptor α and β

Four compounds 1 to 4 (folic acid, methotrexate and 2 dyes) were used to interact with folate receptor (FR)α and FRβ. The interaction structures and binding energies of the bound complexes were investigated. In order to analyze the differences between FRα and FRβ complexes, the details of the weak intermolecular interactions were analyzed, and the frontier orbital properties of the FR complexes were studied by a dispersion complemented density functional tight‐binding method. By comparing the different interaction properties of the 4 compounds with FRα and FRβ, the basic strategies for design of novel compound targeted with FR subtype were suggested. Further, a novel compound with high selectively with FRα based on compound 3 was designed to illustrate our conclusion. These data should be helpful for the design of novel molecules with extreme discerningly with FRα and FRβ.