Study of Complex of AEDG Tetrapeptide with KRH Dendrimer at Two Different pH by Computer Simulation

In previous papers, we studied the behavior of lysine (Lys or K) based dendrimers of the second generation with repeating units KKK and KRR (i.e., with branched neutral lysine and charged double lysine or arginine (KK, RR) spacers). We also studied KLL, KAA, and KGG dendrimers with hydrophobic double leucine, alanine, and glycine (LL, AA, GG) spacers and pH-dependent KHH dendrimers with double histidine (HH) spacers. Their complexes with molecules of several medicinal peptides (including AEDG) were studied as well. It was shown that lysine dendrimers with charged spacers are suitable for the delivery of oppositely charged oligopeptides and genetic material, while dendrimers with hydrophobic internal spacers are good for the delivery of hydrophobic oligopeptides and fullerenes. In the present paper, we study complexes of molecules of AEDG peptide with KRH dendrimer containing arginine-histidine (RH) spacers. In this case, the amino acid residues in the spacer (R and H) of dendrimer are different, and the charge of the H residue depends on pH. We performed molecular dynamics simulations of the complexation of 16 AEDG molecules with a dendrimer at two different pHs: a) KRH at pH>7 with fully uncharged histidines (H) and b) KRHp at pH<5 with fully protonated (Hp) histidines in aqueous solution with explicit counterions. It was found that the dendrimer with protonated histidines forms a more compact complex. KRHp dendrimer can also carry more AEDG tetrapeptide molecules than KRH.