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

Nine novel fluorescent antifolates were designed and docked with FRα and FRβ. For complexes FR-4, FR-5 and FR-6, the binding energies are larger than those of the FR-FOL complexes; For complexes FR-7, FR-8 and FR-9, the difference in binding energy values between FRα-NFA and FRβ-NFA is very large. The RMSD, RMSF and hydrogen bond properties of the bound complexes were studied using molecular dynamics simulations. The primary hydrogen bonds studies demonstrated that the MD and DFTB simulations are qualitatively similar. Considering both the binding affinity and differentiation degree of compound 9, it potently distinguishes FRα from FRβ.88