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Rapid Screening of DNA-Ligand Complexes via 2D-IR Spectroscopy and ANOVA-PCA

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  • Robby Fritzsch
  • Paul M Donaldson
  • Gregory M Greetham
  • Michael Towrie
  • Anthony W Parker
  • Matthew J Baker
  • Neil T Hunt


Publication details

JournalAnalytical Chemistry
DateAccepted/In press - 23 Jan 2018
DatePublished (current) - 20 Feb 2018
Issue number4
Number of pages9
Pages (from-to)2732-2740
Original languageEnglish


Two-dimensional infrared spectroscopy (2D-IR) is well established as a specialized, high-end technique for measuring structural and solvation dynamics of biological molecules. Recent technological developments now make it possible to acquire time-resolved 2D-IR spectra within seconds, and this opens up the possibility of screening-type applications comparing spectra spanning multiple samples. However, such applications bring new challenges associated with finding accurate, efficient methodologies to analyze large data sets in a timely, informative manner. Here, we demonstrate such an application by screening 2016 2D-IR spectra of 12 double-stranded DNA oligonucleotides obtained in the presence and absence of binding therapeutic molecule Hoechst 33258. By applying analysis of variance combined with principal component analysis (ANOVA-PCA) to 2D-IR data for the first time, we demonstrate the ability to efficiently retrieve the base composition of a DNA sequence and discriminate ligand-DNA complexes from unbound sequences. We further show accurate differentiation of the induced-fit and rigid-body binding modes that is key to identifying optimal binding interactions of Hoechst 33258, while ANOVA-PCA results across the full sequence range correlate directly with thermodynamic indicators of ligand-binding strength that require significantly longer data acquisition times to obtain.

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© 2018 American Chemical Society

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