Center on Macromolecular Dynamics by NMR Spectroscopy

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This proposal describes the need for and outline of a Biomedical Technology Research Resource entitled Center on Macromolecular Dynamics by NMR Spectroscopy (CoMD/NMR) and situated at the New York Structural Biology Center. The focus of CoMD/NMR is technical development and application of NMR spin relaxation and associated methods for characterizing protein and nucleic acid conformational dynamics in biological processes including ligand recognition, allosterism, catalysis, and folding. The central challenge addressed by CoMD/NMR is to break down the high activation barrier to using advanced NMR spectroscopic and computational methods and thus to make available the benefits of these sophisticated approaches to the wider biological research community. CoMD/NMR is the platform for meeting this challenge through Technological Research and Development (TR&D) Projects, Driving Biomedical Projects (DBPs), Collaboration and Service, Training, and Dissemination components of the Resource. The TR&D component of CoMD/NMR will develop new and extended methods for characterizing and interpreting macromolecular dynamics, with a strong focus on expanding the general ranges of time scales and masses of targets accessible for study. The dual needs for integrating experimental, computational, and theoretical methods (within the TR&D component) and for interfacing with key biological researchers (within the DBP and Collaboration components) make CoMD/NMR essential. In particular, CoMD/NMR addresses four primary obstacles: (i) future technology developments requires combined advances in sample preparation, NMR hardware and methods development, and integration with computer methods; (ii) access to NMR spectrometers at multiple static magnetic fields, as well as specialty equipment such as dynamic nuclear polarization and field cycling probes, is key to many emerging methods; (iii) transfer of technology to the general biological community has been hindered by the complexity of the methods, absence of integrated pipelines to facilitate data acquisition and analysis by nonspecialists, and lack of infrastructure in individual laboratories to translate these methods for general use; and (iv) biologists with research programs that would benefit from these methods are unaware of this potential and lack expertise to incorporate these approaches into their own research. Technology development proceeds most effectively when driven by challenging applications; accordingly, CoMD/NMR will work closely with outstanding local and national investigators in DBPs designed to motivate and test emerging technology. The resources of CoMD/NMR will be broadly available to the biomedical research community through collaboration and service activities together with expansive training and dissemination programs. The basic research developments of CoMD/NMR will impact a diverse range of biological research with human health relatedness, including degenerative diseases, metabolic disorders, and cancer.