期刊
ANALYTICAL CHEMISTRY
卷 90, 期 4, 页码 2732-2740出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.7b04727
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资金
- STFC [ST/M000125/1]
- BBSRC [BB/L014335/1]
- MRC [MC_PC_16060, MC_PC_17178] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/L014335/1] Funding Source: researchfish
- Medical Research Council [MC_PC_17178, MC_PC_16060] Funding Source: researchfish
- Science and Technology Facilities Council [ST/M000125/1] Funding Source: researchfish
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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