Applications of Parametrized NMR Spin Systems of Small Molecules

Abstract

We have developed technology for producing accurate spectral fingerprints of small molecules through modeling of NMR spin system matrices to encapsulate their chemical shifts and scalar couplings. We describe here how libraries of these spin systems utilizing unique and reproducible atom numbering can be used to improve NMR-based ligand screening and metabolomics studies. We introduce new Web services that facilitate the analysis of NMR spectra of mixtures of small molecules to yield their identification and quantification. The library of parametrized compounds has been expanded to cover simulations of 1H NMR spectra at a variety of magnetic fields of more than 1100 compounds, included are many common metabolites and a library of drug-like molecular fragments used in ligand screening. The compound library and related Web services are freely available from http://gissmo.nmrfam.wisc.edu/.

Low-Field, Benchtop NMR Spectroscopy as a Potential Tool for Point-of-Care Diagnostics of Metabolic Conditions: Validation, Protocols and Computational Models

“…Limitations of databases for authentic biomolecule reference compounds include metabolites predominantly being determined at 500–600 MHz operating frequencies, which could lead to problems with interpreting spectral data at LF. However, the use of NMR-SIM and Guided Ideographic Spin System Model Optimisation (GISSMO) software strategies enables structural calculations, i.e., simulations of spins at different magnetic fields, and can also afford valuable information on both individual molecules and relatively complex mixtures [36,37]. Thus, a combination of databases and simulations are the most appropriate approach for structural elucidation strategies using LF instrumentation.…”

Probabilistic identification of saccharide moieties in biomolecules and their protein complexes

“…Analysis of known saccharide and non-saccharide compounds. 100 non-saccharide chemical compounds were extracted manually from the Maybridge Ro3 fragment library (https://www.maybridge.com/), and their 3D structures were obtained from the GISSMO website 25,30 . CTPIC assigned probabilities of zero to each of these compounds.…”

Automatic 1D 1H NMR Metabolite Quantification for Bioreactor Monitoring

“…They affect the resonance frequency position and intensity of that resonance component. There are existing studies that estimate these parameters from empirical data [ 27 , 28 ], as well as works that simulate the NMR spectrum given these parameters [ 29 ]. See [ 30 ] for a brief guide on how these parameters can help with identifying metabolites, and [ 31 ] for a survey of various methodologies to estimate them.…”