Nucleic Acid Structure and Ligand:DNA Interactions by NMR
Efforts to understand the molecular forces most responsible for the unique double helical structure of DNA have yielded exciting progress in recent years. Studies have been driven both by the desire to understand DNA structure and to expand the genetic code to include numerous non-natural bases incorporated into DNA duplexes. Exciting questions have stemmed from these works. In collaboration with my colleague Debbie Tahmassebi, we are using NMR to investigate the structural details of DNA oligonucleotides containing non-natural bases. Our aims are 1) to characterize the precise helical parameters in the modified duplexes in order to understand the structural factors responsible for duplex stability and 2) to use the sequence-specific binding of ligands to probe DNA recognition, structure and dynamics in the modified duplexes. By these means, we will understand 1) the degree of structural perturbation upon substituting natural nucleosides with novel nonpolar steric mimics; 2) base pair stacking in the region of the modification; 3) base pair opening as a result of modification; and 4) changes in the backbone conformations of the modified duplexes.
Here's a summary of the projects , results and progress in the last few years ...