NMR Fall Symposium

The North Jersey ACS NMR Topical Group proudly presents its October 2014 Symposium at Rutgers Waksman Institute on the Busch Campus in Piscataway on Wednesday, October 22, 2014.  [ register | sponsors ]

Venue

Waksman Institute Auditorium
In the building adjacent to
CABM (Center for Advanced Biotechnology and Medicine)

Rutgers University, Busch Campus
679 Hoes Lane West
Piscataway, NJ 08854   [ map & directions ]

Free parking across the street in unreserved spots.

Program

1:00 pm - Opening remarks

1:05 pm - Robert Griffin

Massachusetts Institute of Technology

“Amyloid, Membranes, Microwaves and MAS”

1:55 pm - Teresa Fan

University of Kentucky

“Exploring Lung Cancer Metabolome: From Bench to Bedside”

2:45-3:15 pm - Coffee break

3:15 pm - Eric Munson

University of Kentucky

“New Applications of Solid-State NMR to Pharmaceuticals”

4:05 pm - Michael Reily

Bristol-Myers Squibb

“Small molecule NMR in Pharma: Using less, doing it quicker and finding biomarkers”

4:55 pm - Marc Caporini

Bruker BioSpin

“Applications of Solid-State NMR using Dynamic Nuclear Polarization with Improved Sensitivity and Fast Acquisition Times.”

5:45 pm - Closing remarks

6:00 - 7:00 pm - Reception - sponsored by Bruker Biospin (in the CABM lobby)

Sponsors

We are grateful to our sponsors for making this symposium possible!

The North Jersey ACS NMR Topical Group proudly presents its September monthly meeting at Rutgers CABM on Wednesday, September 17, 2014. [ register ]

Featured Presentations

"Evolving Approaches to Small Molecule Structure Elucidation"

Robert Thomas Williamson, PhD, Merck & Co.

and

"ASSURE-RMS: Applications to Competitive Intelligence, Detection of Adulteration and Quality Control"

Kimberly L. Colson, PhD, Bruker BioSpin

Program

Abstract:

The North Jersey ACS NMR Topical Group proudly presents its June monthly meeting at Rutgers CABM on Thursday, June 18, 2014. [ register ]

This meeting is sponsored by  ACD Labs

Featured Presentation

 “Auto Structure Verification: Protecting against the Blowback of Compound Errors through Automated and Multi-Spectra Structure Verification“

Philip E. Keyes, Lexicon Pharmaceuticals

Abstract: As the pharmaceutical and materials research industries continue to rely on specialty and custom chemical manufacturers to supply chemical building blocks, fragment libraries and novel investigational compounds for screening, a growing body of evidence points to a systematic failure rate of materials supplied. In general, between 2% to 8% of milligram and gram scale quantities of specialty chemicals have been reported to be incorrect. Recently, the pharmaceutical industry has begun turning to a process called Auto Structure Verification (ASV) by NMR. Based on 1H and 13C NMR chemical shift prediction comparisons to experimental data and automated assignment of atoms to spectrum features, ASV aims to protect against the consequences of errors in supply chain ordered compounds and internal custom syntheses. ASV has the potential to identify nearly 70% – 80% of incorrect isomer structures that LCMS cannot. Recent high profile case studies, such as in C&E News, highlighting incorrectly synthesized Bosutinib sold by third party vendors (Bethany Halford , Bosutinib Buyer Beware, C&E News May 21, 2012, p34) for research benchmark purposes, demonstrate the vulnerability of our discovery programs to supply chain induced synthesis errors. ASV may be helpful in preventing future cases.

The North Jersey ACS NMR Topical Group proudly presents its May monthly meeting at Rutgers CABM on New Date: Thursday, May 29, 2014. [ register ]  Note: This meeting had been scheduled on May 21.

This meeting is sponsored by Aligent Technologies

Featured Presentations

I. “Agilent Technology Overview”

Bill Marathias Ph.D.

NMR Applications Scientist, Agilent Technologies, Inc, Boston MA

II. “NMR, Metabolomics, and Fermentation Process Analysis”

D. Christopher Roe

Corporate Center for Analytical Sciences
DuPont Experimental Station, Willmington, DE

Abstract for Talk II:

Fermentation processes constitute a significant aspect of DuPont’s drive to sustainability and the production of renewably sourced materials. Fermentation process analysis typically involves monitoring selected metabolites and products, and although trends may be discerned, it is hard to know how to relate these observations to overall process performance. In an effort to accelerate fermentation process development, multivariate methods are being applied to combined fermentation and analytical data sets in order to provide an overview of the fermentation process. The goal is to identify differentially expressed metabolites that contribute significantly to the differences between fermentations (e.g., growth variability, high vs. low titer, or one strain vs. another). This information can be assessed for biological significance, and metabolic engineering can be considered for the identified metabolic pathways. The merits of NMR for metabolomic analysis will be described along with data “pre-processing” methods prior to multivariate analysis. A synopsis of multivariate methods will be given and examples of fermentation time course studies will be presented.

The North Jersey ACS NMR Topical Group proudly presents its April monthly meeting at Princeton University on Wednesday, April 16, 2014.  [ register ]

Featured Speaker

“Early stages of protein folding and intrinsic disorder explored by NMR and hydrogen exchange”

Heinrich Roder

Fox Chase Cancer Center, Philadelphia, PA 19111

Abstract:

My talk will focus on our recent applications of NMR and hydrogen exchange for exploring early stages of protein folding and intrinsic disorder. By coupling NMR-detected H/D exchange with ultrafast quenched-flow mixing we have been able to obtain residue-specific structural insight into the ensemble of states populated during the initial stages of folding of cytochrome c (Fazelinia, H.; Xu, M.; Cheng, H.; Roder, H. J. Am. Chem. Soc. 2014, 136, 733-40). The pH-dependence of amide protection, combined with direct measurement of intrinsic exchange rates in the unfolded protein, showed that amide protons in three α-helical segments in the C-terminal half of cytochrome c were preferentially protected from solvent exchange within 100 microseconds of initiating the folding reaction while the N-terminal α-helix remained unprotected. Thus, sequence-local helix-helix contacts are formed preferentially during early stages of folding whereas long-range (N- to C-terminal) become important only during the later stages of folding (> 3 ms). These findings provide compelling evidence that specific structural events rather than a general hydrophobic collapse of the protein chain dominate the initial stages of folding. I will also present recent progress in our studies on the dynamic properties and functional role of intrinsically disordered regions in NHERF1, a 358-residue protein containing a pair of PDZ domains and a C-terminal motif separated by long flexible linkers. Structural and dynamic NMR, along with other biophysical methods, are providing detailed insight into the conformational equilibria and binding properties of this signaling adaptor.

The North Jersey ACS NMR Topical Group proudly presents its February monthly meeting at Rutgers CABM on Wednesday, February 19, 2014.  [ register ]

This meeting is sponsored by Bruker BioSpin

Featured Speaker

“Mapping Protein Folding Landscapes Using High Pressure NMR”

Catherine Royer

Department of Biological Sciences
Rensselaer Polytechnic Institute

Abstract:

Despite significant progress in recent years in understanding protein structural dynamics we still lack sufficient experimental knowledge of protein folding energy landscapes. Moreover, we cannot predict folding transitions states or routes cheapambienpriceonline.com from amino acid sequence or structure. Nor is it known how sequence encodes the conformational fluctuations and heterogeneity required for protein function in specific contexts. We have recently demonstrated that pressure induced unfolding occurs largely because of specific packing defects or void volumes, in the folded structures of proteins that disappear upon unfolding, leading to a decrease in molar volume. Unlike denaturant or temperature perturbations, the effects of which depend on the amount of exposed surface area in the unfolded states of proteins, pressure effects depend on specific properties of folded states. And because packing defects are local and specific, pressure perturbation acts locally to decrease volume, thus allowing for the characterization of intrinsic folding cooperativity. Pressure also provides access to conformational states inaccessible by other methods. Coupling high pressure with multi-dimensional NMR is particularly powerful, as it provides site specific observables throughout the structure of the protein. Used in steady-state and p-jump mode, high pressure NMR has revealed unexpected complexity in the folding rates and routes of cavity-bearing variants of Staphylococcal nuclease. The results underscore the subtlety of the sequence determinants of folding landscapes.
(2 door prizes for # of attendees < 20, 3 door prizes for # of attendees > 20)

The North Jersey ACS NMR Topical Group proudly presents its January monthly meeting at Rutgers CABM on Wednesday, January 22, 2014.  [ register ]

This meeting is sponsored by Bruker BioSpin

Featured Speaker

“Unraveling the Structural Organization of Amyloid with DNP-enhanced MAS NMR Spectroscopy”

Galia Debelouchina, Ph. D.

Princeton University, Princeton, NJ

Abstract:

Amyloid fibrils are insoluble, non-crystalline protein filaments associated with a number of diseases such as Alzheimer’s and Type II diabetes. They can have a functional role in different organisms, and many proteins and peptides have been found to form amyloid fibrils in vitro. This talk will present an overview of what is known regarding their molecular structure, focusing in particular on the fibrils formed by an 11-residue segment from the disease-related protein transthyretin (TTR). This system exemplifies our efforts to characterize the hierarchy of structures present in the fibril form, including the organization of the β-strands into β-sheets (tertiary structure), the β-sheet interface that defines each protofilament (quaternary structure), and the protofilament-to-protofilament contacts that lead to the formation of the complete fibril. Our efforts resulted in the measurement of 110 distance and torsion angle constraints (10 per residue) across all levels of structural organization, resulting in the best resolved amyloid fibril structure so far. The structural investigation benefited extensively from the development of dynamic nuclear polarization, a method used to enhance the sensitivity of MAS NMR experiments, and leading to unprecedented gains in signal-to-noise ratios and acquisition times.

(2 door prizes for # of attendees < 20, 3 door prizes for # of attendees > 20)

The North Jersey ACS NMR Topical Group proudly presents its November monthly meeting at Rutgers CABM on Wednesday, November 20, 2013.  [ register ]

This meeting is sponsored by Bruker BioSpin

Featured Speaker

Talk I

“Protein Dynamics and Biophysical Data Driving Drug Design of Staphylococcus aureus DHFR Inhibitors”

Parag Sahasrabudhe,
CCIE-Structural Biology & Biophysics, Pfizer Global R&D, Groton, CT

Abstract:

DHFR is a classic chemotherapeutic and antibacterial target which has been the subject of numerous structural, protein dynamic and mechanistic studies for over 20 years. A clinically relevant drug resistant mutant, S1 of the Staphylococcus aureus (Sa) ortholog of DHFR has been identified and DHFR inhibitors such as Trimethoprim are about 100-1000 fold less potent against it compared to the wild-type. A loss of enthalpy of interaction between compounds and S1 mutant is detected by isothermal calorimetry. The source of these potency differences are not clearly evident based solely on the low energy static WT and S1 X-ray structures. To address this issue, biophysical methods including NMR solution dynamic studies, in conjunction with thermodynamic, kinetic, computational and structural information are being employed to understand potency differences for both in vitro and whole cell MIC activity studies. Protein dynamics observed by NMR clearly show differences in the binding pockets of WT and S1 proteins as binary and ternary complexes with the cofactor NADPH and Trimethoprim. These differences are not observed in static X-ray structures. Differences observed in us-ms range using relaxation dispersion experiments point to important residues involved in the binding of inhibitor in the substrate binding pocket. Kinetics of binding determined by SPR indicate that the reduction in binding affinities arise from faster off rates and they show correlation to whole cell MICs.

In this presentation, the use of biophysical data to generate hypotheses and to guide chemical design for S1 mutant inhibitors will be highlighted.

The North Jersey ACS NMR Topical Group proudly presents its October monthly meeting at Rutgers CABM on Wednesday, October 23, 2013.  [ register ]

This meeting is sponsored by Bruker BioSpin

Featured Speakers

Talk I

“General Overview of New Products For 2013”

George Anastasi,
Regional sales manager of Bruker BioSpin, Inc.

Talk II

“Recent advances in NMR spectroscopy of encapsulated proteins & nucleic acids dissolved in low viscosity fluids”

Prof. Josh Wand,
Johnson Research Foundation and Department of Biochemistry & Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia

Abstract for Talk II:

Solution NMR spectroscopy is a powerful technique to study protein structure and dynamics on multiple timescales and in many contexts. Sample preparation is often the key ingredient that enables otherwise very difficult studies of complex macromolecular systems. Some time ago we introduced the idea of using solutions of proteins encapsulated within the protective aqueous core of a reverse or inverted micelle and dissolved in low viscosity fluids as a means to overcome the “slow tumbling” problem presented by large, soluble proteins. Since then several advantageous properties of the reverse micelle particle have been used to promote studies of integral and anchored membrane proteins, soluble proteins and nucleic acids of marginal stability as well as investigations of various aspects of protein biophysics such as cold denaturation, protein hydration and protein motion.

Despite this, the approach has not been generally adopted by the NMR community. To make this reverse micelle encapsulation approach more accessible, we have developed an optimized reverse micelle surfactant system. Comprised of the nonionic 1-decanoyl-rac-glycerol and the zwitterionic lauryldimethylamine-N-oxide (10MAG/LDAO), this mixture is found to faithfully encapsulate a diverse set of proteins ranging up to 80 kDa in size and having a broad spectrum of electrostatic properties. Extensive chemical shift analyses indicate that encapsulation conditions that maintain high structural fidelity can be directly found. A clear advantage of 10MAG/LDAO is the active decrease of molecular reorientation time for encapsulated macromolecules larger than ˜20 kDa leading to improved signal-to-noise.

The properties of 10MAG/LDAO are also found to be very favorable for solution NMR studies of lipidated proteins. New and efficient strategies for optimization of encapsulation conditions have also been developed. 10MAG/LDAO performs well in both the low viscosity pentane and ultra-low viscosity liquid ethane and should serve as a general platform for initiating solution NMR studies of proteins and nucleic acids. In a parallel effort, it has been realized that reverse micelle solutions potentially offer a route to implement dynamic nuclear polarization enhancement of protein resonances by avoiding the dielectric heating generally associated with standard aqueous samples. Initial results will be presented. Supported by NSF and the NIH.

The North Jersey ACS NMR Topical Group proudly presents its October 2013 Symposium at Rutgers Waksman Institute on the Busch Campus in Piscataway on Wednesday, October 2, 2013.  [ register ]

Venue:  Waksman Auditorium

In the building adjacent to
CABM (Center for Advanced Biotechnology and Medicine)
Rutgers University, Busch Campus
679 Hoes Lane West
Piscataway, NJ 08854

Free parking across the street in unreserved spots

This program information is also available as a [ flyer ]. Please take a copy and circulate it among your colleagues.

Note there is a $10 registration fee, which we encourage you pay online below (you don’t need a PayPal account!) but it can be paid at the door. Attendance is free for students, retirees, and unemployed. Pre-registration is required to get a head count.