The principal goals of this project are the development of algorithms that allow one to make the best use of NMR data to determine solution structures of biomolecules, to assess in a systematic fashion their accuracy and precision, and to explore the extent to which dynamical information can be extracted from NMR data. This will involve the following components: Studies of conformation-dependent chemical shifts and anisotropies. Ab initio quantum chemistry and empirical calculations will be used to explore patterns of shift anisotropies in peptide and nucleic acid fragments. An initial emphasis will be on 31P anisotropies in nucleic acids and 13CO anisotropies in proteins. Updated refinement methods. Refinement models will be deveoped that use generalized Born solvation models, and which incorporate conformational disorder through the """"""""locally enhanced sampling"""""""" model that uses multiple copies of portions of the macromolecule. Studies on protein and nucleic acid dynamics. Long-time scale molecular dynamics simulations (initially on binase and ribonuclease H) will be used to model NMR relaxaxtion, with attention paid to anisotropic tumbling, to the correlation between internal and overall motions, and to conformational disorder. This will include an analysis of contributions from internal motions to chemical shift anisotropy (CSA) relaxation and to CSA-dipolar cross-correlated relaxation.
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