Automated evaluation of chemical shift perturbation spectra: New approaches to quantitative analysis of receptor-ligand interaction NMR spectra

Journal of Biomolecular NMR
Chen PengSándor Szalma

Abstract

This paper presents new methods designed for quantitative analysis of chemical shift perturbation NMR spectra. The methods automatically trace the displacements of cross peaks between a perturbed test spectrum and the reference spectrum (or among a series of titration spectra), and measure the changes of chemical shifts, heights, and widths of the altered peaks. The methods are primary aimed at the (1)H-(15)N HSQC spectra of relatively small proteins (<15 kDa) assuming fast exchange between free and ligand-bound states on the chemical shift time scale, or for comparing spectra of free and fully bound states in the slow exchange situation. Using the (1)H-(15)N HSQC spectra from a titration experiment of the 74-residue Pex13p SH3 domain with a Pex14p peptide ligand (14 residues, K (d)= approximately 40 microM), we demonstrate the scope and limits of our automatic peak tracing (APET) algorithm for efficient scoring of high-throughput SAR by NMR type HSQC spectra, and progressive peak tracing (PROPET) algorithm for detailed analysis of ligand titration spectra. Simulated spectra with low signal-to-noise ratios (S/N ranged from 20 to 1) were used to demonstrate the reliability and reproducibility of the results when dealing with poo...Continue Reading

Citations

Feb 13, 2007·Journal of Biomolecular NMR·P RavelM A Delsuc
Oct 5, 2012·ACS Nano·Giorgia BrancoliniStefano Corni
Nov 23, 2006·Bioinformatics·Lisa Fukui, Yuan Chen
Oct 1, 2006·Drug Discovery Today. Technologies·Xu ZhangMaili Liu
Jul 10, 2019·Nature Chemical Biology·Jark BöttcherDarryl B McConnell
Apr 14, 2011·Natural Product Reports·Luis P CalleJesús Jiménez-Barbero
Feb 19, 2017·Journal of Biomolecular NMR·Tommaso BanelliAlessandra Corazza

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