UC Riverside

Solid state NMR Spectroscopy is emerging as a mainstream tool in structural biology. Resonance assignments are an essential first step in structural studies, and in the majority of studies to date, these have employed through-space, dipolar correlation spectroscopy. In NMR, it is the scalar or J-coupling interaction that signifies covalent through-bond contact, while the dipolar coupling provides through-space distance constraints. This research involves developing new correlation methods based on scalar-couplings for solid state NMR of proteins.

CTUC COSY, a new scalar-coupling-driven correlation method is introduced which is robust for chemical shift correlation in solids by combining the indirect evolution and transfer periods into a single constant time interval. Both theory and experiment point to distinct advantages of this protocol which was originally motivated by the challenge of obtaining through-bond connectivity in dynamic solids, where global molecular motion renders dipolar-driven correlation methods ineffective, and where liquid-state methodologies proved inapplicable. In this work, it was shown that this new J-MAS method provides substantially increased spectral resolution without compromising sensitivity, which we find to be comparable to or better than the sensitivity of dipolar methods. The results demonstrated that scalar-based methods are sufficiently well developed to serve as a complementary tool to dipolar methods, which will be especially useful for the assignment of large proteins, where resonance overlap presents a major challenge to solid-state NMR.