Small Molecule Accurate Recognition Technology (SMART) to Enhance Natural Products Research

Scientific Reports
Chen ZhangWilliam H Gerwick

Abstract

Various algorithms comparing 2D NMR spectra have been explored for their ability to dereplicate natural products as well as determine molecular structures. However, spectroscopic artefacts, solvent effects, and the interactive effect of functional group(s) on chemical shifts combine to hinder their effectiveness. Here, we leveraged Non-Uniform Sampling (NUS) 2D NMR techniques and deep Convolutional Neural Networks (CNNs) to create a tool, SMART, that can assist in natural products discovery efforts. First, an NUS heteronuclear single quantum coherence (HSQC) NMR pulse sequence was adapted to a state-of-the-art nuclear magnetic resonance (NMR) instrument, and data reconstruction methods were optimized, and second, a deep CNN with contrastive loss was trained on a database containing over 2,054 HSQC spectra as the training set. To demonstrate the utility of SMART, several newly isolated compounds were automatically located with their known analogues in the embedded clustering space, thereby streamlining the discovery pipeline for new natural products.

References

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Citations

Nov 7, 2019·Angewandte Chemie·Brendan M DugganJames J La Clair
Sep 2, 2020·Natural Product Reports·Ruihan ZhangWeilie Xiao
Sep 21, 2019·Current Protocols in Pharmacology·John A Beutler
Aug 1, 2020·Antibiotics·José Diogo SantosOlga Maria Lage
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May 14, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lik Tong Tan, Ma Yadanar Phyo
Jul 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hyun Woo KimYoung-Won Chin
Nov 14, 2020·Journal of Ethnopharmacology·Ngoc-Hieu NguyenWon Keun Oh
Jan 13, 2021·Journal of Cheminformatics·Adrian VoicuVictor Dumitrascu
Mar 1, 2021·Current Opinion in Biotechnology·Stephanie C HeardJaclyn M Winter
May 28, 2021·Journal of Chemical Information and Modeling·Allison S Walker, Jon Clardy
Nov 13, 2020·Analytical Chemistry·Arthur S EdisonSicong Zhang
Feb 12, 2020·Journal of the American Chemical Society·Raphael ReherWilliam H Gerwick
Sep 14, 2019·Journal of Chemical Information and Modeling·Jesse G MeyerAnthony Gitter
Sep 14, 2021·Frontiers in Plant Science·Junelle Rey C Bacong, Drandreb Earl O Juanico
Sep 5, 2021·Magnetic Resonance in Chemistry : MRC·Stefan KuhnRicardo Moreira Borges
Oct 19, 2021·Journal of Natural Products·Hyun Woo KimGarrison W Cottrell

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Methods Mentioned

BETA
nuclear magnetic resonance
NMR
circular
infrared
PCA
X-ray

Software Mentioned

Bokeh
Tensorflow
Matlab
MEM
Photoshop
TopSpin
NUS
hmsIST
SMART
IST

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