Structure and Dynamics of DNA-dendrimer complexation: Role of counterions, water and base pair sequence

TL;DR

This study uses molecular dynamics simulations to explore how DNA sequence, counterions, and water influence the formation and stability of DNA-dendrimer complexes, revealing sequence-dependent effects and complexation mechanisms.

Contribution

It provides a detailed atomistic understanding of DNA-dendrimer complexation, highlighting the role of sequence and molecular interactions in complex stability and formation pathways.

Findings

Stable DNA-dendrimer complexes form with sequence-dependent variations.

Reaction free energy surface exhibits a funnel-like shape with barriers due to misfolded DNA states.

Complexation sensitivity arises from enthalpic and entropic competition in ssDNA.

Abstract

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.