(713a) Using Coarse-Grained Molecular Simulations to Understand Effects of Backbone Chemistry in Oligo-Nucleic Acids on the Thermodynamics of Melting/Hybridization

DNA hybridization is the basis of various bio-nano technologies, such as DNA origami and engineering nanostructures from assembly of DNA-functionalized nanoparticles. A hybridized double stranded DNA is formed when complementary nucleobases on two single strands of oligo-nucleotides exhibit highly specific and directional hydrogen bonds with each other through canonical Watson-Crick base-pairing interactions (G-C, A-T) and neighboring bases on same strand exhibit base-base stacking. In recent years the need for cheaper alternative and significant synthetic advances have allowed for design of DNA mimics by incorporating new backbone chemistries to either modify or replace the sugar and phosphate groups found in DNA. However, a fundamental understanding of how these backbone modifications in the oligo-nucleic acids impact the hybridization and melting behavior of the double strands is still lacking. In this talk, we will present our recent findings on impact of varying backbone chemistry, specifically impacting backbone charge and flexibility, on hybridization and stability of oligo-nucleic acid duplexes. We will first describe our coarse-grained model that captures the essential melting trends seen with dsDNA. We will then describe simulation results obtained using these models that present the impacts of strand flexibility, electrostatic and dispersion interactions on the melting curves as a function of G-C content, strand length and concentration.