An automated fragmentation quantum mechanics/molecular mechanics approach (AFNMR) has shown promising results in chemical shift calculations for biomolecules. Trends in chemical shift are stable with regards to change in density functional or basis sets, and the use of the small “pcSseg-0” basis, which was optimized for chemical shift prediction, opens the way to more extensive conformational averaging, which can often be necessary, even for fairly well-defined structures. There have also been recent advances in the use of machine learning approaches to develop empirical connections to structure. I will discuss prospects for using both types of calculations to gain insights into biomolecular structure and dynamics.  [ slides ]

In this presentation I will review advances in the detection of surfaces and interfaces using solid-state NMR and how these techniques have been applied in materials science. In particular, I will discuss NMR signal enhancement using cross-effect dynamic nuclear polarization (DNP), as well as methods for generating non-equlibrium electron spin polarization optically with nitrogen-vacancy (NV) centers in diamond and designer chromophore-radical systems.  [ slides ]

Recent advances in structural biology have dramatically expanded the scope of proteins and assemblies that are now amenable to structural analysis. Yet, many biological systems display dynamics and undergo transformations that have been difficult to capture experimentally, especially in complex or native settings. In this context, my group has been developing NMR-based methodologies to describe such challenging systems and to pave the way to the next exciting structural biology frontier, the cellular environment. Here, I will present our progress on two fronts: 1) Development of NMR methodologies to describe the molecular basis of protein phase transitions from the liquid to the gel and solid states. In particular, I will focus on the transitions displayed by heterochromatin protein 1α (HP1α), a key player in gene regulation and chromatin organization. 2) Development of sensitivity-enhanced NMR approaches suitable for the cellular environment. Our work is based on a methodology called dynamic nuclear polarization (DNP) which can transfer polarization from electron to nuclear spins and thus increase nuclear signals by several orders of magnitude. For this purpose, we develop small molecule DNP polarization agents that contain unpaired electron spins and that can be targeted selectively to a protein of interest. These agents have allowed us to obtain NMR structural data of tiny amounts of proteins (1-5 μg) and to study the  polarization transfer mechanisms in targeted DNP experiments. [ slides ]

Solid-state NMR can be used to measure atomic-resolution structure and chemical kinetics in a broad range of systems, including those that lack periodicity, have defects, or otherdisorders. I will dicuss biophysics studies where detailed local conformational information is attenable despite long-range (nm-µm) disorder. I will highlight our recent study of TIA1, aprotein involved in several neurodegenerative diseases. Even in this large (43kDa) and complex protein, we could obtain site-specific information necessary for understanding the protein’s mechanisms and ligand binding. I will also discuss several Solid-state NMR methods development projects. I will introduce a class of recoupling pulse sequences that use an “interleaving” scheme to tune effective Hamiltonian scaling factors. [ slides ]

Many functional inorganic and biological materials are also highly complex in structure and composition on length scales of nanometers or greater. Solid state NMR is particularly well-suited to study these materials, due to its ability to observe local structure and site-specific dynamics. In this talk, I will share how solid-state NMR can be used to reveal new details about complex materials ranging from crystalline, porous metal-organic frameworks (MOFs) to arthropod silk and bacterial biomass. I will also describe new developments in solid state NMR instrumentation, including a new paradigm for magic-angle spinning (MAS) experiments: spherical MAS rotors. [ slides ]

Nuclear magnetic resonance, with focus on hyperpolarization. Responsibility for product development in dissolution DNP, parahydrogen, brute-force hyperpolarization and other emerging methods in nuclear spin hyperpolarization. Leading internal R&D and external co-development and testing through customer collaborations. [ slides ]

TBA

NMR as a whole, but especially solid-state NMR, can be classed as a “signal-limited” technique – with limited sample volumes, compromises must be made between signal-to-noise ratio and experimental acquisition times. In recent years, a sensitivity revolution has enabled orders-of-magnitude signal enhancements, up to a theoretical maximum of 660- fold, via the Dynamic Nuclear Polarization (DNP) technique. In enabling the gradual easing of the aforementioned compromises, DNP-enhanced SSNMR has enabled studies of systems not previously amenable to solid-state NMR, including whole viruses, amyloid fibrils, membrane proteins, and complex multi-component materials. Yet, the “there is no such thing as a free lunch” mantra also applies — DNP-NMR is not without its pitfalls, generally requiring specialized hardware and modifications to the sample that can impact spectral resolution. Extensive efforts have gone into mitigating these pitfalls and maximizing the sensitivity gains available, especially as the field moves to ever higher magnetic fields. Recent investigations of previously under-explored facets of the technique, for instance direct enhancement of nuclei other than 1H, hint that we have only scratched the surface in terms of the capabilities and potential of DNP. In this talk, I will present:

• An overview of the technology and mechanisms behind DNP, including recent advances at high magnetic field and low microwave power
• A brief practical discussion of the state-of-the-art in sample preparation for various DNP applications
• Recent work in 19F-DNP, with potential implications for the field as a whole
• Perspectives for the future: combining DNP, ultrafast magic angle spinning (MAS), and selective excitation to revolutionize sensitivity and resolution

Structural details often provide molecular mechanisms to construct the interplay among biology, chemistry and engineering for drug product development. Solid-state NMR analyzes a wide range of drug and wet pharmaceutical materials from small molecule medicines to biological products. The obtained structural information at macroscopic and microscopic scales offer critical knowledge for understanding and optimizing drug delivery, chemical and physical stability, bioavailability, formulation composition, and manufacturing process. This presentation will provide examples to introduce the molecular structure mediated questions in pharmaceutical sciences and elaborate how ssNMR techniques are employed to tackle these analytical challenges.