RM1 Center on Macromolecular Dynamics by NMR Spectroscopy at the New York Structural Biology Center (CoMD/NMR)- Equipment Supplement Request - This proposal describes the mission and strategic plans for of a Biomedical Technology Development and
Dissemination Center (RM1) entitled Center on Macromolecular Dynamics by NMR Spectroscopy
(CoMD/NMR). Located at the New York Structural Biology Center, CoMD/NMR has developed new
experimental and computational techniques in NMR spectroscopy, including both structure and dynamics
methods for both solution and solid state NMR. Here we focus mainly on spin relaxation methods, which have
already had great impact for characterizing protein and nucleic acid conformational dynamics during biological
processes including ligand recognition, allosterism, oligomerization, catalysis, and folding. The central
challenge addressed by CoMD/NMR is to break down the high activation barrier for new users to apply
advanced NMR spectroscopic and computational methods and thereby make sophisticated NMR approaches
available to a wide biological research community. To do so, CoMD/NMR addresses four primary obstacles.
(i) Because dynamics problems for biopolymers are frequently underdetermined, we develop incisive new
experiments, pulse sequences and computational methods.
(ii) Because access to advanced NMR instruments can be a limitation for many users, we provide access
to a range of enabling NMR instrumentation, including NMR spectrometers at multiple static magnetic
fields, a range of modern probes, dynamic nuclear polarization, rapid-freeze-quench, high-pressure
equipment, and field cycling relaxometry, all in a well maintained, staff supported, and multiuser
environment.
(iii) Because transfer of technology to biologists (and even to NMR spectroscopists) has been hindered by
the complexity of the methods, and since time efficient use of the instruments is crucial, we develop
robust efficient pipelines to facilitate experimental planning, data acquisition and analysis by non-
specialists.
(iv) Because biologists with research programs that would benefit from these methods are unaware of the
potential, we engage in community outreach and education.
A unique strength of our program is the integration of forefront solid state NMR, solution NMR and
computational experts, and this proposal highlights synergy across these approaches. Additionally, being
situated within the NYSBC, we have excellent partnerships with X-ray diffraction, Cryo EM, and membrane
protein production technologies. Given the demanding nature of the three Technology Development Projects
(TDPs) proposed herein, we have identified a number of Technology Partnership Projects (TPPs), engaging
world leaders in aspects of NMR who have indicated their eagerness to partner with us. Technology
development proceeds most effectively when driven by exciting and challenging applications; accordingly,
CoMD/NMR will work closely with outstanding local and national investigators through Collaborative and
Service Projects (CSP), Driving Biomedical Projects (DBB) and Community Engagement (CE) activities,
including extensive training and dissemination programs. Through its various components, CoMD/NMR will
impact a diverse range of biological research with human health relatedness, including degenerative diseases,
metabolic disorders, and cancer.
