Workshops – Saturday July 25, 2020

AMWS1 – 3D Structure Elucidation of Natural Products Using a Combination of Isotropic/Anisotropic NMR Parameters and Computational Methods – $30 with Registration
9:00 AM – 12:00 PM
Roberto R. Gil (Carnegie Mellon University)
R. Thomas Williamson (UNC Wilmington)
The molecular constitution of most small molecules can in principle be straightforwardly determined by manual or automatic analysis of a set of 2D NMR data from experiments of homonuclear/heteronuclear through-bond correlations, in combination with their molecular formula. At this point, only atomic connectivities are established but no information about the spatial arrangement the them is known (Molecular Configuration/Conformation). This is the primary concept embedded in conventional CASE (Computer Assisted Structure Elucidation) protocols.[1] Once the constitution has been established, the determination of the relative configuration and preferred conformation is a more challenging task and was historically addressed in NMR by using NOE and proton-proton and proton-carbon 2,3J coupling constants analysis. The affordable access to fast and parallelized computing processors made molecular modeling and DFT calculations of NMR parameters (chemical shifts / J coupling constants) more accessible to the scientific community. In the group of anisotropic NMR parameters, the development of the application of Residual Dipolar Couplings (RDCs) and Residual Chemical Shift Anisotropy (RCSA) to the configurational and conformational analysis of small molecules has matured enough in the recent years to perform this task in an almost straightforward way. To complete the configurational/conformational analysis of small molecules, these parameters can be used individually, as needed, in order to solve a particular structural problem, or can be combined in multi-NMR parameter fitting protocol to select the correct configuration/conformational space from a complete set of computer-generated diastereoisomers. The latter is known as Computer-Assisted 3D Structure Elucidation (CASE-3D) protocol.
We assume that attendees know how to determine molecular constitution and to perform NMR assignments. The scope of the current workshop is to provide the attendees with state-of-the-art tools to confirm the 2D structure proposals and determine the 3D structure (configuration and conformational space) of small molecules in general. We will also provide tips about computational parameters.
The workshop will cover the following topics in detail and from very practical standpoint to determine configuration and conformational space:
    • Application of 1H and 13C isotropic chemical shift
    • Scalar coupling constant (J) based analysis using a variety of J proton-proton and proton-carbon
    • Residual Dipolar Couplings (RDCs) and Residual Chemical Shift Anisotropy (RCSA): sample preparation, data collection and data analysis.
    • 1D and 2D Quantitative Nuclear Overhauser Enhancement (NOE)
    • Multi-NMR parameters fitting to computer generated structures (CASE-3D)

AMWS2 – Young Members Workshop – $15 with Registration
Part I – Career Opportunities for NP Chemists beyond Natural Products in the Biotech / Pharmaceutical Industry (Panel Discussion)
Part II – CV Preparation and Interview Skills 
9:00 AM – 12:00 PM
The ICNPR 2020 Young Members workshop will feature a panel discussion by professionals who were trained in natural products research, but who work in industries in which their acquired skills have been applied to other areas, such as biotech and other industries. They will share their perspectives and insights about exploring opportunities and developing careers for natural products chemists in disciplines beyond natural products research.    It is highly notable that as of now, three Vice-Presidents of local companies have agreed to participate in this panel (other panelists will be added).   Another part of this workshop will include CV preparation and interview skills, given by people who have experience in hiring staff for companies, those with experience in reviewing faculty applications, and individuals who have experience reviewing graduate and postdoctoral fellowship applications.   This workshop will be extremely valuable for anyone contemplating employment in the near future.

PMWS1 – A Practical Workshop on New Approaches to Improving the Clinical Translation of Early Phase Natural Product Research – $30 with Registration
2:00 PM – 5:00 PM
Barbara Sorkin (NIH/Office of Dietary Supplements)
Mahtab Jafari (University of California Irvine)
Adam J. Kuszak (NIH/Office of Dietary Supplements)
Michael A. Walters (University of Minnesota)
Mario Ferruzzi (North Carolina State University)
John MacMillan (UC Santa Cruz)
Guido F. Pauli (University of Illinois at Chicago)
If you are interested in adding new techniques to improve the translational or clinical relevance of your natural product (NP) research, then you may find this workshop useful. Speakers will discuss the importance and implementation of good NP research practices that were addressed at a workshop at the US National Institutes of Health (NIH) in September, 2018. The ICNPR workshop will delve further into topics of relevance to the ICNPR community, such as new approaches to the generation of strong mechanism of action hypotheses, bioinformatic tools for analyzing information-rich biological data sets, critical controls for non-specific effects of NP in in vitro assays, considering the effects of human diversity on pharmacokinetics, and use of invertebrate models for NP research.

PMWS2 – Using the Small Molecule Accurate Recognition Technology (SMART) Tool – $30 with Registration
2:00 PM – 5:00 PM
William Gerwick (University of California, San Diego)
Hyunwoo Kim (University of California, San Diego)
Raphael Reher (University of California, San Diego)
Chen Zhang (University of California, San Diego)
Kelsey Alexander (University of California, San Diego)
This hands-on workshop is focused on teaching the use of the NMR-based automatic structure classification tool known as Small Molecule Accurate Recognition Technology (SMART). This new tool is based on the training of a deep convolutional neural network with 1H-13C HSQC spectra; as such, when presented with a new 1H-13C HSQC spectrum for an unknown compound, it very rapidly places this compound in multidimensional space close to other compounds with similar 1H-13C HSQC spectra.  The format of 1H-13C HSQC data for making a query to SMART will be illustrated, and the querying of this unknown in the SMART tool through a webserver will be demonstrated.  The application of SMART to mixture analysis as well as noise reduction will also be shown.  Using 1H-13C HSQC spectra of the user, or samples provided by the workshop organizers, participants will conduct their own query of the SMART, and will explore the relationship of their unknown to known molecules in the SMART database. Finally, illustration of the SMART universe in true 3D will be provided using a Visual Reality tool. The course is suitable to anyone with a basic background in NMR spectroscopy and interest in natural products structure determination.  Participants should bring a computer, be able to connect to the internet, and optionally have tabulated HSQC data listing only proton and associated carbon shifts for protonated carbon atoms (see the  website for more detailed instructions).