TDP1: Chemical exchange and relaxation dispersion techniques for functional hotspots

Chemical exchange phenomena in NMR spectroscopy arise when kinetic or conformational dynamic processes change the magnetic environment of a spin, typically on time scales slower than rotational diffusion in solution (the situation is even more complicated in solid-state NMR spectroscopy). In many systems that have been described in the literature, chemical exchange phenomena are observed on biologically relevant time scales and at “hotspot” regions of a macromolecular structure. The long-term aim of TDP1 is to provide an integrated platform for application to diverse biological problems and encompasses;

  1. Development of theoretical approaches for describing multi-site dynamical processes in solution and solid-state NMR rotating-frame experiments.

  2. Development of novel relaxation dispersion experimental methods in solution and solid-state NMR spectroscopy.

  3. Integration of software to facilitate planning, analysis and dissemination of chemical exchange studies.

A major effort at CoMD/NMR has been the development of the open-source RING software package. This program allows data analysis and simulation of CEST, CPMG, and R1ρ solution NMR experiments, using a number of different two-state theoretical models using modern statistical methods. In TDP1, refinement of RING continues extending capabilities to solid-state NMR rotating-frame relaxation experiments based on Model Free expressions, as well as N-site kinetic models based on numerical simulations. A key aspect of software development efforts in all TDPs is integration of a pipeline from data acquisition to final analysis (allowing seamless information flow from spectra to peak intensities to relaxation rate constants to dynamical parameters) that incorporates “expert knowledge” to increase accessibility to non-expert laboratories, which frequently do not contain specialists in NMR spin relaxation and associated techniques.