Resurgence of magnetic resonance techniques in the era of AlphaFold.

Structural biology has seen the evolution of multiple pioneering experimental techniques over the last few decades, with leaps in technology and software facilitating rapid solution of crystal structures and the 'resolution revolution' in cryo-electron microscopy. Higher magnetic field strengths have expanded the development of magnetic resonance techniques and their ability to study protein dynamics and conformational diversity. Moreover, decades of experimental data collection and public data deposition combined with modern machine-learning technology have now made it possible to computationally predict three-dimensional protein structures from their amino acid sequence within minutes using AlphaFold (AF), a feat that has inspired a new wave of research. AlphaFold now contributes towards experimental structure solution and provides plausible predictions for structured regions of proteins leaving dynamics and conformational exchange as the next major questions in the field. Nuclear magnetic resonance (NMR) spectroscopy is uniquely placed both to rapidly validate AF predictions and probe protein dynamics at an atomic level in solution. Electron paramagnetic resonance (EPR) spectroscopy can measure distances between specific points in large protein complexes and provide local and global ranges of movement. This review will explore the revival of magnetic resonance techniques in a post-AlphaFold landscape and address their importance in protein research.