Molecular Dynamics Studies of the Size and Internal Structure of the PAMAM Dendrimer Grafted with Arginine and Histidine

G4 PAMAM dendrimers with each of the 64 termini grafted with zero to three histidine (His) residues followed by an end-grafted arginine (Arg) were simulated at two levels of protonation to mimic their electrostatic charges at pH 5 and 7. Arg is cationic at both pH values, and His is cationic only at pH 5. The simulations were carried out with a coarse-grained (CG) dendrimer force field that had previously predicted sizes and pH-dependent transitions between dense-core and dense-shell structures that were in agreement with experiments and all-atom simulations. In the work reported here, conjugation with Arg alone slightly increases the size of the dendrimer-conjugate complex at both pH 5 and 7 relative to that of the unmodified G4 dendrimer. Additional conjugation with His (pKa of ∼6.0), and with Arg again at the dendrimer terminals, does not change the complex size at pH 7 (at which His is neutral) relative to that with Arg alone, but at pH 5 (at which His is cationic), the addition of His does increase d...