All atomistic molecular dynamics simulations were performed on poly(amidoamine)(PAMAM) dendrimers that compound non-covalently with anticancer drug molecules including DOX,MTX,CE6,and SN38.The binding energies as well as their associated interaction energies and deformation energies were combined to evaluate the relative binding strength among drug,PAMAM,and PEG chains.We find that the deformation of dendrimers due to drug loading plays a crucial role in the drug binding.It is energetically favorable for the drug molecules to bind with PAMAM while the drugs bind with PEG metastable chains via kinetic confinement.Surface PEGylation helps dendrimers to accommodate more drug molecules with greater strength without inducing too much expansion.This work indicates that tuning the functionalized terminal groups of dendrimers is critical to design efficient dendrimer-based drug delivery systems. All atomistic molecular dynamics simulations were performed on poly (amidoamine) (PAMAM) dendrimers that compound non-covalently with anticancer drug molecules including DOX, MTX, CE6, and SN38. The binding energies as well as their associated interaction energies and deformation energies were combined to evaluate the relative binding strength among drug, PAMAM, and PEG chains. We find that the deformation of dendrimers due to drug loading plays a crucial role in the drug binding. It is energetically favorable for the drug molecules to bind with PAMAM while the drugs bind with PEG metastable chains via kinetic confinement. Surface PEGylation helps dendrimers to accommodate more drug molecules with greater strength without inducing too much expansion. This work indicates that tuning the functionalized terminal groups of dendrimers is critical to design efficient dendrimer-based drug delivery systems.