ac7b02884_si_001.pdf (1.12 MB)
Spin System Modeling of Nuclear Magnetic Resonance Spectra for Applications in Metabolomics and Small Molecule Screening
journal contribution
posted on 2017-10-23, 00:00 authored by Hesam Dashti, William M. Westler, Marco Tonelli, Jonathan R. Wedell, John L. Markley, Hamid R. EghbalniaThe
exceptionally rich information content of nuclear magnetic
resonance (NMR) spectra is routinely used to identify and characterize
molecules and molecular interactions in a wide range of applications,
including clinical biomarker discovery, drug discovery, environmental
chemistry, and metabolomics. The set of peak positions and intensities
from a reference NMR spectrum generally serves as the identifying
signature for a compound. Reference spectra normally are collected
under specific conditions of pH, temperature, and magnetic field strength,
because changes in conditions can distort the identifying signatures
of compounds. A spin system matrix that parametrizes chemical shifts
and coupling constants among spins provides a much richer feature
set for a compound than a spectral signature based on peak positions
and intensities. Spin system matrices expand the applicability of
NMR spectral libraries beyond the specific conditions under which
data were collected. In addition to being able to simulate spectra
at any field strength, spin parameters can be adjusted to systematically
explore alterations in chemical shift patterns due to variations in
other experimental conditions, such as compound concentration, pH,
or temperature. We present methodology and software for efficient
interactive optimization of spin parameters against experimental 1D-1H NMR spectra of small molecules. We have used the software
to generate spin system matrices for a set of key mammalian metabolites
and are also using the software to parametrize spectra of small molecules
used in NMR-based ligand screening. The software, along with optimized
spin system matrix data for a growing number of compounds, is available
from http://gissmo.nmrfam.wisc.edu/.