“Enabling Enhanced Sensitivity in nD-NMR by Non-Uniform Sampling: Theory and Applications”
Abstract:
In the rapidly expanding use of non-traditional data acquisition
and processing for multi-dimensional NMR, the intrinsic sensitivity
of these approaches has been overlooked or misleadingly reported.
We recently solved exact analytic theory for the intrinsic sensitivity
of exponentially weighted non-uniform sampling (NUS) of decaying
signals and find that enhancements from 1.3-2.2 fold are possible
in two-dimensional NMR, which present opportunities to be compounded
in 3D-NMR. The predicted gains are carefully demonstrated by
experiments on many compounds including challenging biological
samples in both liquids and solids. We will show that NUS changes
the detection limit of nD-NMR and delivers actual enhancements that
begin to approach the gains netted by cryogenic probes.
II.
Jeffrey C. Hoch, Ph.D.
Professor of Molecular, Microbial, and Structural Biology
Director, Gregory P. Mullen NMR Structural Biology Facility
Director, University of Connecticut Partnership for Excellence in Structural Biology,
University of Connecticut Health Center
“Maximum Entropy Reconstruction of Nonuniformly Sampled Multidimensional NMR Data”
Abstract:
In the rapidly expanding use of non-traditional data acquisition
and processing for multi-dimensional NMR, the intrinsic sensitivity
of these approaches has been overlooked or misleadingly reported.
We recently solved exact analytic theory for the intrinsic sensitivity
of exponentially weighted non-uniform sampling (NUS) of decaying
signals and find that enhancements from 1.3-2.2 fold are possible
in two-dimensional NMR, which present opportunities to be compounded
in 3D-NMR. The predicted gains are carefully demonstrated by
experiments on many compounds including challenging biological
samples in both liquids and solids. We will show that NUS changes
the detection limit of nD-NMR and delivers actual enhancements that
begin to approach the gains netted by cryogenic probes.
III.
Luciano Mueller
Bristol Myers Squibb
“Characterization of ligand binding to a G-protein coupled receptor”
Abstract:
Reductive methylation of lysine residues permitted the introduction
of 13C-labels in samples of β2 adrenergic receptor – a member
of an important class of drug discovery targets - the G protein
coupled receptors. Indirect detection of 13C-methylated lysine
residues enabled monitoring of ligand-induced modulations of the
salt bridge between lys305 & asp192 at the interface of the
extra-cellular loops 2 & 3. This salt bridge contributes to the
formation of a cavity on the extra cellular surface of the receptor.
The extra-cellular surface adjacent to this NMR-detectable K305 :
D192 salt bridge may be amenable to the design of subtype-specific
exosite modulators of β2 AR activity, and may prove an attractive
venue for overcoming the challenge of designing subtype specific
β2 AR modulators. Distinction between highly mobile and structurally
restrained lysine methyls was achieved via saturation transfer
filtered hc hmqc and hc hsqc experiments.
Door Prizes!
Place: Fuji Japanese Sushi & Seafood
1345 US Rt 1, North Brunswick, NJ 08902
Please note that Pathmark is no more. Fuji is on US 1 Southbound.
