Development of experimental techniques to study protein and nucleic acid structures

This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This research project sought to develop experimental tools for structural biology, specifically those applicable to three-dimensional, biomolecular-structure analysis. Most biological systems function in solution environments, and the ability to study proteins and polynucleotides under physiologically relevant conditions is of paramount importance. The authors have therefore adopted a three-pronged approach which involves crystallographic and nuclear magnetic resonance (NMR) spectroscopic methods to study protein and DNA structures at high (atomic) resolution as well as neutron and x-ray scattering techniques to study the complexes they form in solution. Both the NMR and neutron methods benefit from isotope labeling strategies, and all provide experimental data that benefit from the computational and theoretical tools being developed. The authors have focused on studies of protein-nucleic acid complexes and DNA hairpin structures important for understanding the regulation of gene expression, as well as the fundamental interactions that allow these complexes to form