Novel fluorescent antifolates that target folate receptors α and β: Molecular dynamics and density functional theory study.

Nine novel fluorescent antifolates, 1-9, were designed and docked with FRα and FRβ. The binding energies of the bound complexes were determined by molecular docking and MM-PBSA studies. The structural properties of the complexes FR-FOL, FR-7, FR-8 and FR-9 were analyzed in detail via molecular docking and molecular dynamics studies. We further calculated the root mean square displacement and root mean square fluctuation of the bound complexes using molecular dynamics simulations. Since compounds 7, 8 and 9 are promising candidate in distinguishing FRα from FRβ, the hydrogen bond properties of complexes FRα-7, FRα-8 and FRα-9 were studied by a dispersion complemented density functional tight-binding method. The purpose of this study is to provide a rationale for the design of novel fluorescent antifolates targeted with FRα and FRβ.