This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Solution X-ray scattering has a promise of becoming very useful for structural investigation of systems such as large non-globular macromolecular assemblies, multi-domain proteins, or inherently flexible or disordered macromolecules. The central goal of this proposal is to create a methodology for a very accurate calculation of wide-angle scattering profiles from macromolecular atomic coordinates for a combined application with solution NMR for investigation of structure and dynamics. We are concentrating on macromolecular systems for which the highest quality structural solution NMR models are available, along with the extensive dynamical information, including protein G, ubiquitin, lysozyme, calmodulin and Dickerson dodecamer B-DNA. We are assuming that the average macromolecular geometry for these systems is known exactly and any discrepancies between the calculated and observed scattering profiles are to the deficiencies of the scattering data prediction. We will obtain explicitly calculated displaced solvent form factors from accurate bulk water distributions in place of the solvent-corrected atomic form factors which will afford us a more accurate prediction of the wide-angle scattering intensity. We will also incorporate a representation of the atomic motions in the macromolecule into the calculation of the scattering profile using extensive solution NMR data on the dynamics of the listed proteins. Finally, we will improve scattering data modeling by constructing inhomogeneous three-dimensional distributions of the solvent surrounding the macromolecule that reflect the compositions of the proteins surfaces and best-fit the scattering data. The methodology will be validated on Dickerson dodecamer B-DNA for which the positions of the bound waters are well known.
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