The National Magnetic Resonance Facility at Madison (NMRFAM) recently purchased a small angle X-ray scattering (SAXS) system on a shared instrumentation grant. The technology we propose to develop here will take advantage of this system and integrate SAXS data into our methodology for NMR investigations of larger proteins and RNA molecules. We propose to pursue additional lines of research not covered by the parent grant P41 RR02301 with the goal of integrating new tools into our platform for supporting key collaborative research projects. Aim 1 proposes to develop applications of the fast maximum likelihood reconstruction algorithm (Newton) developed by Dr. Roger Chylla, who was not funded by the parent grant at the time of its renewal. The goals are to integrate Newton into tools for high-throughput screening of solution conditions and automated analysis of ligand binding to proteins. In addition, we plan to use Newton to improve the robustness of spectral peak recognition in NMRFAM's platforms for data collection and automated spectral assignment. Aim 2 proposes to reactivate our collaboration with Dr. Hamid Eghbalnia (University of Cincinnati) through a subcontract to the University of Cincinnati. This collaboration had been funded by a separate grant, which has lapsed. The aim will be to use advanced mathematical approaches to develop a next generation platform for integrated protein data collection and analysis, including structure determination. The Eghbalnia laboratory has developed a much improved method (TAFL^) for deriving protein backbone torsion angle restraints from chemical shifts, and we propose to use this information to improve the determination of protein structures from sparse data. Aim 3 has the goal of integrating SAXS data with information from residual dipolar couplings (RDCs) and NOE spectra into software for automated structure determination. Aim 4 proposes an analogous approach for automated structure determination of RNA molecules. The technology developed will be disseminated through the NMR center (NMRFAM) and will be made publically available.