NMR in the Age of Modern Biomedical Research and Drug Discovery.

Abstract

The success of artificial intelligence for structure prediction has led to forecasts of a reduced need for experimental structural biology. Here, we focus on nuclear magnetic resonance (NMR) spectroscopy and its various applications to biomedical research, including and extending beyond structural biology. As a structural tool, NMR is highly complementary to X-ray crystallography and cryo-electron microscopy (cryo-EM) and uniquely suited for studies of intrinsically disordered and dynamic systems in real time. It produces spectral fingerprints of biomolecules at the atomic scale to provide information on the structure, interactions, and motions that occur in solution. We focus on the power of NMR to characterize moderately sized dynamic systems, identify and validate the binding of small molecule ligands to biomolecular targets, and its capacity to further develop and be empowered by artificial intelligence-based structural prediction software. Experimental structural biology begins with sample preparation, and we present recent advancements for overcoming hurdles associated with reconstitution of biological systems for NMR studies and ongoing challenges, including in the application of NMR for cell-based research. NMR is aptly suited to bench-to-bedside efforts for its ability to do metabolomic profiling and follow drug response. We present the capacity of NMR to delve into complexities that are the foundation of biological function and focus on its ongoing challenges and opportunities to apply NMR for the advancement of biomedical research.