(521f) Coarse-Grained Molecular Simulation Studies of Melting Thermodynamics of Oligonucleic Acids Conjugated with Polymers

Hybridization and melting of duplexes of nucleic acid oligomers (or oligonucleic acids, ONA) is the basis of various bio- and nano- technologies, such as DNA origami, toe-hold displacement, antisense therapy, etc. Hybridization of two ONA single strands into a duplex is driven by specific and directional hydrogen bonds between complementary bases on the two ONA strands and base-base stacking between neighboring bases on the same ONA strand. The stability of the resulting duplex is quantified through features of ONA melting curves, namely, sharpness of the duplex melting and the melting temperature. These features of the ONA melting curves are impacted by the ONA strand length, ONA base sequence and composition, ONA backbone chemistry, solvent quality, salt concentration, etc. Additionally, conjugation of ONA single strands with other substrates/particles/macromolecules can also impact the resulting ONA duplex stability. In this talk, we present the effect of solvent quality on the polymer conjugated to ONA strands on the ONA duplex stability. We conduct our study with molecular dynamics simulations using a coarse-grained model recently developed in our group; this coarse-grained model is capable of capturing the specific and directional H-bonds driving ONA hybridization, while also enabling simulations at larger length scales and time scales than possible with atomistic models. We find that varying the polymer-solvent effective interactions non-trivially shifts the melting temperature to higher or lower values depending on the ONA backbone design (e.g. charged or neutral) and solvent quality (e.g. poor or good solvent).