Effect of oligonucleic acid (ONA) backbone features on assembly of ONA–star polymer conjugates: a coarse-grained molecular simulation study

Abstract

Understanding the impact of incorporating new physical and chemical features in oligomeric DNA mimics, termed generally as “oligonucleic acids” (ONAs), on their structure and thermodynamics will be beneficial in designing novel materials for a variety of applications. In this work, we conduct coarse-grained molecular simulations of ONA–star polymer conjugates with varying ONA backbone flexibility, ONA backbone charge, and number of arms in the star polymer at a constant ONA strand volume fraction to elucidate the effect of these design parameters on the thermodynamics and assembly of multi-arm ONA–star polymer conjugates. We quantify the thermo-reversible behavior of the ONA–star polymer conjugates by quantifying the hybridization of the ONA strands in the system as a function of temperature (i.e. melting curve). Additionally, we characterize the assembly of the ONA–star polymer conjugates by tracking cluster formation and percolation as a function of temperature, as well as cluster size distribution at temperatures near the assembly transition region. The key results are as follows. The melting temperature (T_m) of the ONA strands decreases upon going from a neutral to a charged ONA backbone and upon increasing flexibility of the ONA backbone. Similar behavior is seen for the assembly transition temperature (T_a) with varying ONA backbone charge and flexibility. While the number of arms in the ONA–star polymer conjugate has a negligible effect on the ONA T_m in these systems, as the number of ONA–star polymer arms increase, the assembly temperature T_a increases and local ordering in the assembled state improves. By understanding how factors like ONA backbone charge, backbone flexibility, and ONA–star polymer conjugate architecture impact the behavior of ONA–star polymer conjugate systems, we can better inform how the selection of ONA chemistry will influence resulting ONA–star polymer assembly.