DYNAMIC MACROMOLECULAR STRUCTURES IN SOLUTION VIA ANALYSIS OF NMR EXPERIMENTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the past few years, three-dimensional structures of about 200 small proteins and a DNA oligomers in solution have been determined. Multi-dimensional NMR, in particular two-dimensional nuclear Overhauser effect(2D NOE) spectra, when used in conjunction with distance geometry and energy refinement calculations can be used to determine the high-resolution structure of DNA fragments, small proteins and complexes. A major goal of our research is to improve the capability for determining high-resolution protein and nucleic acid structures in solution, including a depiction of their dynamic nature. To this end, we have been developing methods to obtain more accurate structural restraints(in the form of internuclear distances and torsion angles) and a greater number of structural restraints. We are currently working on new refinement protocols using restrained molecular dynamics and the particle mesh Ewald technique as implemented in the sander module of AMBER 5.0. In addition, as we deal mostly with conformationally flexible molecules in solution, we have been exploring computational methodologies for ascertaining the dynamic nature of these molecules. Publications - Konerding DE, Cheatham TE 3rd, Kollman PA, James TL.:"Restrained molecular dynamics of solvated duplex DNA using the particle mesh Ewald method.":Journal of Biomolecular Nmr:13:119-31:1999; Achievements - We used the T3E at PSC to run a 2 nanosecond unrestrained MD simulation of DNA in explict solvent using AMBER 5.0. See publication #1 below for more details. Publications - None that have not previously been reported.