Research
Our work is in biophysical chemistry, primarily using NMR to investigate properties of damaged DNA. DNA is a fundamentally dynamic molecule, and local conformational properties may play significant roles in interactions with other molecules (biomolecular recognition). More specifically, we are looking for differences in conformational properties (local dynamics and structure) between normal and damaged DNA using NMR and other types of spectroscopy. We then hope to extrapolate to determine what (if any) functional role these properties play in recognition by repair proteins such as DNA glycosylases.
As is common in science, we have interests in many areas and collaborate with colleagues on development of novel materials for gene transfer, and combining Raman scattering with computational chemistry.
Recent Publications
M. N. Westwood, A. Pilarski, C. Johnson, S. Mahmud, and Gary A. Meints, “Backbone Conformational Equilibrium in Mismatched DNA Correlates with Enzyme Activity,” Biochemistry 2023, 62 (19), 2816–2827. https://doi.org/10.1021/acs.biochem.3c00230
M. N. Westwood, C. C. Johnson, Nathan A. Oyler, and Gary A. Meints, “Kinetics and thermodynamics of BI-BII interconversion altered by T:G mismatches in DNA," Biophysical J. (2022), https://doi.org/10.1016/j.bpj.2022.03.031
M. N. Westwood, K. D. Ljunggren, Benjamin Boyd, Jaclyn Becker, Tammy Dwyer, and Gary A. Meints, “Single Base Lesions and Mismatches Alter the Backbone Conformational Properties in DNA,” Biochemistry 2021, 60, 873-885. https://dx.doi.org/10.1021/acs.biochem.0c00784
Bakker, M., Boyd, B., and Meints, G. A., “3D Printed NMR spectra: From 1D and 2D acquisition to 3D visualization,” Concepts in Magnetic Resonance A, 2019;47A:e21470, published online April 2, 2019, https://doi.org/10.1002/cmr.a.21470.
Dou, X., Meints, G. A., and Sedaghat-Herati, R., “New Insights into the Interactions of a DNA Oligonucleotide with mPEGylated-PAMAM by Circular Dichroism and Solution NMR,” J. Phys. Chem. B. 2019. 123 (3); 666-674.
Pederson, K., Echodu, D. C., Emani, P., Olsen, G. L., Bardaro, M. F., Shajani, Z., Meints, G. A., Miller, P. A., Varani, G., and Drobny, G. P., “Unifying Solution and Solid-State NMR Studies of Nucleic Acid Dynamics,” in Encyclopedia of Magnetic Resonance (R. K. Harris and Wasylishen R. E., eds.), Chichester: John Wiley, Mar. 2010.
Kinde-Carson, M., Ferguson, C., Oyler, N. A., Harbison, G., and Meints, G. A., “Solid State 2H NMR Analysis of Furanose Ring Properties in DNA Containing Uracil,” J. Phys. Chem. B, 2010, 114, 3285–3293.
Hardin, J. L., Oyler, N. A., Meints, G. A., and Steinle, E. D., “Spectroscopic Analysis of Interactions between Alkylated Silanes and Alumina Nanoporous Membranes,” Journal of Colloid and Interface Science, 2010, 342, 614–619.
Videos
Below are some recorded videos relating to our work.
Using Nuclear Magnetic Resonance (NMR)
We use multiple types of NMR experiments to determine site-specific properties of DNA. H - P HSQC's show how backbone phosphate peaks are affected by the presence of a single base lesion.
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Base damage alters local DNA dynamics and structure.
NMR spectra can be extrapolated to calculate families of DNA structures leading to an average structure, which indicate regions of specific structural or dynamic alterations.
Energetics of damaged DNA
From the P spectra, we observe changes to the free energy landscape of DNA backbone interconversion due to the presence of single base lesions.
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Other projects
We are working with colleagues to investigate interactions between mPEGylated dendrimers and DNA, as well as using computational chemistry to comprehensively determine the Raman vibrational transitions of DNA nucleosides.
