Coarse-grained molecular simulation studies of effect of solvent quality on melting thermodynamics of oligonucleic acids (ONA) and ONA-polymer conjugates

Hybridization or melting thermodynamics of oligomers of nucleic acids (e.g., DNA, RNA, PNA) duplexes is dependent on oligonucleic acid (ONA) backbone chemistry, length, base sequence and composition, and solvent chemistry. Understanding how solvent quality affects ONA stability, in free state and when conjugated to polymers is important for use of ONA in nucleotide-based bio- and nano- technologies. In this talk, I will present our recent molecular simulation work using a coarse-grained model capable of capturing the specific and directional H-bonds between complementary bases in ONA, in implicit solvents. We found that, as the solvent quality worsens for the polymers conjugated to neutral and flexible ONAs (such as PNA), the ONA melting temperature increases for all the ONA sequences, G-C content and polymer length studied. For negatively charged and semi-flexible ONAs (DNA-like), the conjugation of longer solvophobic polymer (as compared to ONA length) decreases the ONA melting temperatures while conjugation of relatively shorter solvophobic polymer, similar to ONA length, does not affect melting temperatures for all the ONA sequences and G-C content studied.