Natural Products


  • Establishing the relative configuration of a bioactive natural product represents the most challenging part in determining its structure.
  • NMRFAM developed a protocol for structural analysis of complex natural products to include Residual Dipolar Couplings (RDCs) in addition to NOE and the J-based analysis. For complex compounds (e.g. natural products), the use of only later two leads to hundreds of possible configurations and corresponding structures, and this ambiguity can be lifted if RDCs are added to the analysis. Unlike all published methods that use RDCs to elucidate a molecule’s configuration, our method does not require any DFT model.  In fact, we highlight the shortcomings of using DFT models in conjunction with RDCs measured in solution: sometimes DFT models with different configurations fit poorly or equally well the experimental RDCs or, for more dynamic molecules, no DFT model would fit the experimental RDCs within their experimental errors
  • We adapted a force field structure calculation methodology to allow free sampling ofboth R and S configurations of the stereocenters of interest. The algorithm uses a floating alignment tensor in a simulated annealing protocol to identify the conformations and configurations that best fit experimental RDC and distance restraints (from NOE and J-coupling data).
  • The novelty of our method does not reside in simply using RDCs for determining the structure and configuration of small molecules, but in the unique and simple way of doing it, in contrast with the time consuming (e.g. for Ecteinamycin, with 14 chiral centers, generating up to 213 DFT models is also computationally intensive), and sometimes complex ways this has been done in all published studies to date, particularly in the cases of molecules with flexible parts and/or with conformational heterogeneity (that required computing exhaustive DFT models, MD simulations, computing conformational models, establishing conformer populations, filtering conformers based on experimental data, etc.). For the all literature cases analyzed we proved that our method matched the accuracy of the published methods using a vastly simpler approach.
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Cornilescu G, Ramos Alvarenga RF, Wyche TP, Bugni TS, Gil RR, Cornilescu CC, Westler WM, Markley JL, Schwieters CD Wyche TP, Alvarenga RFR, Piotrowski JS, Duster MN, Warrack SR, Cornilescu G, De Wolfe TJ, Hou Y, Braun DR, Ellis GA, Simpkins SW, Nelson J, Myers CL, Steele J, Mori H, Safdar N, Markley JL, Rajski SR, Bugni TS

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Biochemistry 800 - Practical Nuclear Magnetic Resonance Theory 

Biochemistry 801 - Biochemical Applications of Nuclear Magnetic Resonance 

"The Future of NMR-Based Metabolomics, Current Opinion in Biotechnology (2017), pp. 34-40

Documents on the use of the Bruker-Axs Nanostar,SAXS instrument and analysis of SAXS data are now available.

NMRFAM-SPARKY Distribution - the popular NMR analysis program SPARKY recompiled (including updated python and Tcl/Tk) with incorporation of PINE-Sparky, enhancements to import/export to the structural analysis program CYANA, and other useful python extensions.

ADAPT-NMR Enhancer: Complete Package for Reduced Dimensionality in Protein NMR Spectroscopy

RNA-PAIRS: RNA Probabilistic Assignment of Imino Resonance Shifts

PACSY, a Relational Database Management System for Protein Structure and Chemical Shift Analysis 

 

Donate to NMRFAM. US tax-deductible donation can be made to NMRFAM
Please write check payable to "UW Foundation, Account 112152802"  
And mail to: 
Attn: Sarah Lynn Traver Saunders
Associate Administrative Program Specialist 
University of Wisconsin-Madison 
433 Babcock Drive 
Madison, WI 53706 
Tel: 608-265-2507 or email 

 

1st: Lai Bergeman 
Rm 171; Phone 262-3173

2nd: Milo Westler
Rm B160; Phone 263-9599

3rd: Paulo F. Cobra
Rm B224; Phone 265-3303

4th: Marco Tonelli
Rm B160; Phone 263-9493

5th: John Markley
Rm 171A; Phone 263-9349

We welcome your questions and feedback!

NMRFAM Established 1987