Design of Macromolecular Biomaterials Using Atomistic and Coarse-Grained Molecular Simulations

In this talk, I will present our recent work using molecular simulations to design novel oligonucleic acids (ONAs) with varying backbone chemistries to tune ONA hybridization and melting. Since double stranded DNA (ds-DNA) is the basis of various bio- and nano- technologies, the need for cheaper alternatives and significant synthetic advances have led to the design of DNA mimics with new backbone chemistries (e.g. click nucleic acids, locked nucleic acids). 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. We use coarse-grained (CG) and atomistic molecular dynamics simulations along with well-tempered metadynamics calculations to capture the effects of varying backbone chemistries on the H-bonding between complementary nucleobases and the intra-strand base-base stacking, and ONA hybridization/melting. I will also present our recent results on how conjugation of these novel ONAs with biocompatible polymers (e.g. PEG) impacts the polymer-conjugated ONA hybridization. These polymer-conjugated ONAs will serve as building blocks for thermo-responsive gels and networks in biomaterials.