Interacted mechanism of functional groups in ligand targeted with folate receptor via docking, molecular dynamic and MM/PBSA.

Twenty novel compounds with different functional groups (-COOH, -OH, -NH2 and -CH3) were designed to study the interaction mechanism of ligands with folate receptors (FRs). The optimized structure and the dipole moment of the novel compounds were calculated by a density functional tight-binding method (DFTB). The binding mechanism of the compounds with FRs was studied by molecular docking, molecular dynamic (MD) simulations and MM/PBSA free energy calculations. The binding energies, root mean square displacement and root mean square fluctuation of the complexes were analyzed to further illustrate the effect of the functional groups. The functional groups play important roles in stabilizing the bound complexes. Compared to other groups, -OH is more stably linked with the compound. These data provide a theoretical basis for the design of novel compounds targeted with FRs.