NMRmix: A Tool for the Optimization of Compound Mixtures in 1D (1)H NMR Ligand Affinity Screens.
 

NMRmix: A Tool for the Optimization of Compound Mixtures in 1D (1)H NMR Ligand Affinity Screens.

Related Articles NMRmix: A Tool for the Optimization of Compound Mixtures in 1D (1)H NMR Ligand Affinity Screens.

J Proteome Res. 2016 Mar 11;

Authors: Stark JL, Eghbalnia HR, Lee W, Westler WM, Markley JL

Abstract
NMR ligand affinity screening is a powerful technique that is routinely used in drug discovery or functional genomics to directly detect protein-ligand binding events. Binding events can be identified by monitoring differences in the one-dimensional (1)H NMR spectrum of a compound with and without protein. Although a single NMR spectrum can be collected within a short period (2-10 min per sample), one-by-one screening of a protein against a library of hundreds or thousands of compounds requires a large amount of spectrometer time and a large quantity of protein. To improve the efficiency of these screens in both time and material, compounds are usually evaluated in mixtures ranging in size from 3 to 20 compounds. Ideally, the NMR signals from individual compounds in the mixture should not overlap so that spectral changes can be associated with a particular compound. We have developed a software tool, NMRmix, to assist in creating ideal mixtures from a large panel of compounds with known chemical shifts. Input to NMRmix consists of a (1)H NMR peak list for each compound, a user-defined overlap threshold, and additional user-defined parameters if default settings are not used. NMRmix utilizes a simulated annealing algorithm to optimize the composition of the mixtures to minimize spectral peak overlaps so that each compound in the mixture is represented by a maximum number of non-overlapping chemical shifts. A built-in graphical user interface simplifies data import and visual evaluation of the results.


PMID: 26965640 [PubMed - as supplied by publisher]



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