Structure and Dynamics of DNA−Dendrimer Complexation: Role of Counterions, Water, and Base Pair Sequence

We study sequence-dependent complexation between oligonucleotides (single-strand DNA) and various generation ethylene diamine (EDA) cored poly amido amide (PAMAM) dendrimers through atomistic molecular dynamics simulations accompanied by free energy calculations and inherent structure determination. Simulations reveal formation of a stable complex and provide a detailed molecular level understanding of the structure and dynamics of such a complexation. The reaction free energy surface in the initial stage is found to be funnel-like, with a significant barrier arising in the late stage due to the occurrence of misfolded states of DNA. Complexation shows surprisingly strong sensitivity to the ssDNA sequence, which is found to arise from a competition between enthalpic versus entropic rigidity of ssDNA.