The chemical shift of an atom is a direct result of the atom's environment. This valuable source of data goes unused in most NMR structure refinement methods, however. The goal of this research is to develop theories that relate chemical shifts to three dimensional conformation, so that macromolecular structures of improved quality can be more speedily attained. The approach is as follows: A pool of experimental chemical shifts will be gathered for small compounds and macromolecules for which detailed structural information is known. Additional shifts will be generated for small molecules or complexes of interest, using recently developed quantum chemistry techniques. Empirical equations approximating the physical effects of environment on chemical shifts will be developed and parameterized to match the collected data. Once satisfactory equations are obtained, they will be integrated into a structure refinement program. In addition to accelerating and improving NMR refinement methods, this work will pinpoint areas in biomolecules where solution and crystal structures differ, by way of discrepancies between observed and calculated shifts. Ultimately, this knowledge may aid in the understanding of structurally-related mechanisms of biomolecular function.
