Fritzsch, Robby, Donaldson, Paul M, Greetham, Gregory M et al. (4 more authors) (2018) Rapid Screening of DNA-Ligand Complexes via 2D-IR Spectroscopy and ANOVA-PCA. Analytical Chemistry. pp. 2732-2740. ISSN 0003-2700
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 American Chemical Society |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 01 Feb 2019 10:30 |
Last Modified: | 27 Dec 2024 00:12 |
Published Version: | https://doi.org/10.1021/acs.analchem.7b04727 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1021/acs.analchem.7b04727 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:141901 |