Session TOA. There are 5 abstracts in this session.

Session: Molecules and Medicines, time: 08:30-8:55
Principles of protein structural ensemble determination
Michele Vendruscolo
University of Cambridge, Cambridge, United Kingdom
Since the biological functions of protein molecules are intimately dependent on their conformational dynamics, structural ensembles offer useful representations of their states. I will describe how the well-established principles of protein structure determination should be extended to the case of protein structural ensembles determination. These principles concern primarily how to deal with conformationally heterogeneous states, and with experimental measurements that are averaged over such states and affected by a variety of errors. I will finally illustrate the application of these principles by describing the characterisation of the differences in the structural ensembles of the 40 and 42 residue variants of the amyloid beta peptide using chemical shifts and residual dipolar couplings.

Session: Molecules and Medicines, time: 08:55-9:20
How NMR can help in small molecule drug discovery 
Harald Schwalbe
University Of Frankfurt, Frankfurt, Germany
NMR spectroscopy is a key technique to support structure based drug discovery. In this presentation, I will show how NMR is the key analytical method, as technique to analyse fundamental binding mechanism (orthosteric or allosteric) and to rapidly derive key insight in the structural and dynamic contributions to binding.

Session: Molecules and Medicines, time: 09:45-10:00
Atomic-Resolution Map of the Interactions between Amyloid Inhibitors and Beta Amyloid (Aβ) Peptides in the Monomer and Protofibril States 
Giuseppe Melacini
McMaster University, Hamilton, Canada
Self-association of beta amyloid (Aβ) peptides is a hallmark of Alzheimer’s disease and serves as a general prototype for amyloid formation. A multitude of Aβ self-association inhibitors is currently available, ranging from exogenous low MW ligands, such as the EGCG catechin, to endogenous extracellular chaperone-like proteins, such as Human Serum Albumin (HSA). However, the molecular mechanism by which these amyloid inhibitors bind and remodel Aβ monomers and oligomers is not fully understood. Here, we show how 15N and 1H dark-state exchange saturation transfer (DEST), in combination with 15N T2 and CHemical Shift Covariance Analyses (CHESCA) NMR experiments can be utilized to map the interactions of amyloid inhibitors with the surface of nanoparticle-like Aβ oligomers (MWaggregate~1MDa) and with Aβ monomers.

Session: Molecules and Medicines, time: 10:00-10:15
Characterization of Protein-Ligand Interactions Using Multichannel Detection of Hyperpolarized 19F Spins
Mengxiao Liu; Yaewon Kim; Christian Hilty
Texas A&M University, College Station, Texas
Nuclear magnetic resonance (NMR) spectroscopy has long been used to characterize protein-ligand interactions. Recently, hyperpolarization techniques have been developed to increase the intrinsic low sensitivity of NMR by several orders of magnitude, and therefore achieve fast acquisitions and low concentration requirements. Here, we demonstrate that a single aliquot of a ligand hyperpolarized by dissolution dynamic nuclear polarization can be split and measured via multichannel NMR spectroscopy. This multichannel detection can be used to measure chemical exchange dynamics and improve the throughput of binding affinity screening.

Session: Molecules and Medicines, time: 9:20-9:45
Unequivocal determination of 3D molecular structures using proton residual chemical shift anisotropy
Nilamoni Nath1; Juan Carlos Fuentes1; Michael Reggelin2; Christian Griesinger1
1Max Planck Institute for Biophysical Chemistry, Gottingen, Germany; 2Technical university of Darmstadt, Darmstadt, Germany
Determination of 3D molecular structure remains a challenging task for natural products or organic compounds that are in the range of a few 10 µg. It is because NOE and J couplings are not sufficient to establish the relative configuration in chiral natural products and RDCs or carbon RCSAs are difficult to collect because of low sensitivity. Herein, we report robust measurement of 1H RCSAs by using constrained aligning gel or liquid crystal and their utilization in determining the complex 3D molecular structures of several molecules with varying complexities.