Atomistic molecular dynamics (MD) simulations of a G4-NH(2) PAMAM dendrimer were carried out in aqueous solution using explicit water molecules and counterions (with the Dreiding III force field optimized using quantum mechanics). Our simulations predict that the radius of gyration (R(g)) of the dendrimer changes little with pH from 21.1 A at pH approximately 10 (uncharged PAMAM) to 22.1 A at pH approximately 5 (charged with 126 protons), which agrees quantitatively with recent small angle neutron scattering (SANS) experiments (from 21.4 A at pH 10 to 21.5 A at pH 5). Even so we predict a dramatic change in the conformation. The ion pairing in the low pH form leads to a locally compact dense shell with an internal surface area only 37% of the high pH form with a dense core. This transformation from "dense core" at high pH to "dense shell" at low pH could facilitate the encapsulation and release of guest molecules (e.g., drugs) using pH as the trigger, making dendrimers a unique drug delivery vehicle.

PAMAM Dendrimers Undergo pH Responsive Conformational Changes without Swelling