Session PD. There are 12 abstracts in this session.

Session: THEORY / COMPUTATION, poster number: 215

Efficient Approaches for Addressing Spectral Ambiguities in Computer Assisted Structure Elucidation (CASE) Systems

Nicola Kuter; Rostislav Pol; Mikhail Elyashberg; Sergey Golotvin; Dimitris Argyropoulos
Advanced Chemistry Development, Toronto, Canada

Computer Assisted Structure Elucidation (CASE) systems have significantly facilitated de novo structure elucidation of both natural and synthesized organic compounds. They are, however, susceptible to a series of limitations which impede structure elucidation by a human expert. These limitations are mainly associated with the ambiguity of the experimental data which significantly increases both the size of the output and the time of structure generation. Using recent programming developments, we present approaches that enable structure elucidation under conditions where the initial data contains many ambiguous assumptions. Examples will be shown to highlight the strengths as well as the limitations of each approach.

Session: THEORY / COMPUTATION, poster number: 216

Novel and Robust NMR-based Conformational Analysis to Advance 3D Structure Characterization of Cyclic Peptides

Qi Gao1; Xiao Wang1; Yizhou Liu1; Edward Sherer1; Ajay Jain2; Mikhail Reibarkh1
1Merck & Co. Inc., Kenilworth, NJ; 2University of California, San Francisco, CA

The interest of peptide drug therapeutics has significantly increased for their potential to interact with challenging biological targets. We will demonstrate a newly developed approach featuring rapid determination of high-resolution 3D conformation of cyclic peptides in solution using a small number of NMR restraints with an advanced conformational sampling mechanism. This complementary approach yields high-quality peptide solution ensembles in the cases where traditional NMR-based calculation methods have been either very time-consuming or unsuccessful. It is applied to elucidate the 3D conformation of aureobasidin A, a cyclic depsipeptide antifungal. A minor conformer of aureobasidin A, where proline adopts a cis configuration on the peptide bond, has also been successfully elucidated for the first time.

Session: THEORY / COMPUTATION, poster number: 217

Designing Specific Inhibitors to target S100B in Melanoma

Darex Vera-Rodriguez; Brianna Young; Shardell Spriggs; Wenbo Yu; Paul T. Wilder; Alexander D. Mackerell; David J. Weber
University of Maryland, Baltimore, Baltimore, MD

Malignant melanoma (MM) is defined as the most dangerous form of skin cancer. Previous studies demonstrate S100B as a tumor marker in MM, a protein that interacts with the tumor suppressor p53, inhibiting p53 function. This project aims to identify S100B-specific small molecule inhibitors and understand the basis of their specificity over other S100 family members (specifically S100A1). To identify S100B-specific compounds, a 2D-[1H,15N] NMR HSQC fragment-based screening approach and Site-Identified Ligand Competitive Saturation (SILCS) molecular dynamics (MD) simulations were performed with S100B and S100A1. Results show a novel hydrophobic pocket in Ca2+-bound S100B comprised by residues involved in binding to a S100B-specific fragment. These data provide important information relevant to developing S100B-specific drugs to treat MM. 

Session: THEORY / COMPUTATION, poster number: 219

CoMD/NMR: Software for Analysis of NMR Relaxation Data

Martha A. Beckwith1; Teddy Erazo-Colon1; Arthur G. Palmer III2; Bruce A. Johnson1
1CUNY ASRC, New York, NY; 2Columbia University, New York, NY

Molecular motions are fundamental to the existence of life, and NMR spectroscopy remains one of the most useful and powerful methods to measure their rates and molecular characteristics. The complexity of the data analysis has led to multiple groups developing a wide variety of different software packages for each type of experiment. CoMD/NMR is a new program that combines the tools for analyzing multiple types of relaxation experiments in a single GUI. Written primarily in Java and Python, it is a cross-platform application that runs on Linux, Mac OS X, and Windows, and supports analysis of data from T1, T2, CPMG, CEST, and R1ρ experiments.

Session: THEORY / COMPUTATION, poster number: 220

Backbone resonance assignment of large proteins by NMR fingerprinting of peak shapes

Paul Coote1, 2; Scott Robson1, 3; Abhinav Dubey1, 2; Haribabu Arthanari1, 2
1Dana-Farber Cancer Institute, Boston, MA; 2Harvard Medical School, Boston, MA; 3Indiana University, Bloomington, IN

NMR resonance assignment of large proteins is challenging due to crowded spectra and rapid relaxation. We address these difficulties by boosting the information content of the experiments with the highest intrinsic sensitivity. Optimized decoupling pulses produce “fingerprint” patterns in the peak shapes that encode the chemical shifts of additional spins. The new information comes without more coherence-transfer delays and encoded dimensions. The observed patterns are decoded to reveal chemical shift frequencies of coupled spins. The advantage is to exploit high-sensitivity experiments (HNCA) but obtain information about bonded nuclei (CB and C') without additional relaxation. We have empirically confirmed fingerprint patterns are observable over a range of relevant protein sizes (6-180 kDa), including large proteins.

Session: THEORY / COMPUTATION, poster number: 221

Sensitivity Gain in non-uniformly Sampled NMR Experiments

Yulia Pustovalova; Jeffrey C. Hoch
UConn Health, Farmington, CT

The emergence of nonuniform sampling (NUS) in NMR allowed acquisition of spectra at high resolution and/or dimensionality that cannot be obtained with traditional uniform sampling (US). Additionally, time saved by skipping sampling points can be used to increase the number of scans and so improve sensitivity, which is particularly important for low concentration protein samples. However, comparison of sensitivity in data sets recorded with different parameters and/or processing algorithms can be challenging when there is no US spectrum available. Here we systematically explore the sensitivity in 15N-NOESY-HSQC of the 31kDa protein PfPMT. We compare uniformly sampled data with NUS data sets with different sparsity and number of scans. Our results offer insights for improving experiment design for sensitivity-limited samples.

Session: THEORY / COMPUTATION, poster number: 222

One-Bond 13C Satellite Suppression in 2D NMR

Arika Hisatsune; Peter Kiraly; Mathias Nilsson; Gareth Morris
University of Manchester, Manchester, United Kingdom

The recent DISPEL (Destruction of Interfering Satellite by Perfect Echo Low-pass Filtration) method suppresses one-bond 13C satellite signals without the need for broadband 13C decoupling. Here it is concatenated with TOCSY to yield TOCSY spectra with one-bond 13C satellite signals suppressed in F2, and full 13C decoupling in F1. The new pulse sequence is illustrated with experimental spectra showing clean suppression of 13C satellites. The approach is generally applicable, it being possible to concatenate a wide variety of multidimensional NMR methods with DISPEL at very low cost in signal-to-noise ratio, and should make it significantly easier to analyse the spectra of high dynamic range mixtures by 1H NMR.

Session: THEORY / COMPUTATION, poster number: 223

Spin Scenario: A unified scripting environment for MR practitioner

Yan Chang1; Daxiu Wei2; Steffen Glaser3; Xiaodong Yang1
1SIBET, Chinese Academy of Sciences, Suzhou, China; 2East China Normal University, Shanghai, China; 3Technical Univ. Munich, Garching, N/A
Numerical simulation of spin dynamics is essential for kinds of studies, and there have been many excellent open source packages such as Spinach, SIMPSON, SpinDynamica, etc. Recently we released a new simulation package, Spin Scenario, which offers the MR practitioner a unified scripting environment in a “plug-and-play” format that provides a new, flexible and intuitive pulse sequence programming syntax for rapid sequence prototyping.  The Spin Scenario is also provided as an open-source project (, and has been demonstrated to be able to perform NMR/MRI simulations and shaped pulses optimization.

Session: THEORY / COMPUTATION, poster number: 224

Use of Floquet-Magnus Expansion and Fer Expansion Approaches to Control the Spin Dynamics during the Spin- Locking Radiation in NMR

Eugene Mananga; Richard Ametepey; willmar Ulloa; Paulin Dongomale
The City University of New York, New York City, NY
We compare two very close methods that are developing in the field of solid-state NMR, namely the Floquet-Magnus expansion and the Fer expansion approaches. Both approaches can be obtained from the method of canonical transformations with different systems of canonical transformations, which correspond to the study of spin dynamics in different frames of reference. We use these expansion schemes for the calculation of effective Hamiltonians and propagators. We present an important iterative approach for the Floquet-Magnus expansion. While both approaches are powerful methods, there are subtle differences among them. To understand these differences, we performed explicit calculations for the multiple-pulse spin-locking experiment. Our work unifies and generalizes existing results of Floquet-Magnus and Fer approaches and delivers illustrations of novel springs.

Session: THEORY / COMPUTATION, poster number: 225

Low-Field NMR Spectroscopy with Spin-Lock Induced Crossing

Stephen DeVience
Scalar Magnetics, LLC, Cuyahoga Falls, OH

Proton NMR spectroscopy of organic molecules at low magnetic fields typically produces only a single spectral line devoid of identifying information, making it unsuitable for most analytical purposes. This study demonstrates an alternative form of spectroscopy using SLIC (spin-lock induced crossing). It shows that J-coupling spectroscopy can be performed on most organic molecules without the typical need for a heteronucleus. Based on the location and strength of spectral dips that occur at level anti-crossings during weak spin-locking, 1D and 2D spectra can be acquired and used to identify molecules whose conventional NMR spectra at low field appear indistinguishable. Simulations of spin chains, halogenated benzenes, and other molecules finds complex J-coupling spectra promising for spectral fingerprinting.

Session: THEORY / COMPUTATION, poster number: 226

A New Twist on Calculating Chemical Exchange Dynamics: Application to SABRE

Jacob Lindale; Shannon Eriksson; Warren Warren
Duke Unviversity, Durham, 0

Signal Amplification By Reversible Exchange, or SABRE, is derives large nuclear spin polarization from the singlet order of parahydrogen. While pyridine is the basis for nearly every theoretical model for SABRE, none of these models have the computational efficiency to carry out the simulation on the explicit SABRE system, which in the case of 15N-pyridine has 14-coupled spins. By re-interrogating the underlying assumptions that lead to the incorporation of the exchange interaction in magnetic resonance, we construct a highly accurate and computationally efficient master equation model for SABRE capable of explicitly calculating SABRE systems. We do so without neglecting critical effects, such as nonlinear rebinding dynamics and relaxation, making our model singly capable in the design of new SABRE experiments.

Session: THEORY / COMPUTATION, poster number: 227

Solution state structural and dynamics studies of Skp1 reveals unique mechanism of interaction in SCF ubiquitin E3 ligase 

Amrita Bhattacharya
IIT BOMBAY, Mumbai, India


The S-phase kinase-associated protein 1 (Skp1) is an adapter protein in the multi-protein SCF (Skp1-Cullin-1-F-box) ubiquitin E3 ligase complex. Skp1 recognizes and binds to the F-box protein (FBP), which in turn binds and presents the substrate meant for degradation to the rest of the E3 ligase. Skp1 binds to the conserved F-box domain of the FBP via  its C-terminal helices H6, H7 and H8. FBPs are the only variable component of the SCF complex and thereby determine the substrate specificity. Many of these FBPs along with Skp1are implicated in cell cycle dysregulation, DNA damage,cancer along with several other diseases. Therefore, the Skp1-Fbox domain interface is a potential new drug target.