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Faculty Research

  • Andrew J. Nieuwkoop
  • Andrew J. Nieuwkoop
  • Assistant Professor
  • Research Synopsis: Magic angle spinning solid-state NMR of proteins, membranes, and materials.
  • Phone: (848) 445-2626

 

Research

The Nieuwkoop lab focuses on solid-state NMR, along with solution NMR, X-ray scattering, and molecular dynamics simulations to probe the physical chemistry of ionic liquids, study membrane proteins and lipids of importance to human health, and develop methods to characterize materials and pharmaceuticals. We focus on methods development and combining information from multiple sources to access samples that would otherwise be hard to investigate. The unifying theme is that the atomic resolution insight provided by solid-state NMR is vital for expanding our understanding of the large-scale behaviors of complicated systems.

Lipids and Membranes

Lipid membranes are key to the integrity of all cells and the location of many key biological processes. The Nieuwkoop Lab focuses on the lipid bilayer itself, an area underrepresented in the field of structural biology despite the importance of the lipid environment and composition for essential cellular functions. NMR is one of the only ways to understand how the properties of a lipid bilayer affect and are affected by the proteins they interact with. I am particularly interested in the signaling lipids phosphatidylinositol phosphates (PIPs). PIPs are key regulators of important signaling networks, giving them relevance to cancer, diabetes, and a myriad of specific genetic disorders. I develop proton detected hardware and methods to measure membrane bound samples and novel 31P NMR experiments to characterize phosphate group dynamics in biologically relevant settings.

Lipid-Protein Interactions

The most straightforward way lipids affect the activity of proteins is through direct interactions. NMR can monitor these interactions by tracking changes in the lipid or protein chemical shifts. Because of the challenges of studying them in their native lipid environment, much of what we know about their structure and function comes from samples in detergent or bilayer mimetics. My group studies kindlin-2 (K2), a peripheral membrane protein and a component of the cytosolic side of the integrin transmembrane receptor complexes essential for cellular adhesion. We are investigating the structural basis of K2 binding to PIPs in the membrane to understand how specific lipid interactions control its activity.

Ionic Liquids

Ionic liquids (ILs) are made from mixtures of relatively small organic ions that are liquid at room temperature. They possess high ionic conductivity and low vapor pressure which make them useful for pressing challenges like battery design and green chemistry applications. The relevant macroscopic properties of these materials are tied to nanoscopic transport and structural phenomena. NMR can monitor the structure and dynamics of every atom in a molecule, making it a natural choice for the study of these liquids. By combining NMR and X-ray scattering my lab is developing novel approaches to interrogate the relevant phenomena that define transport and structure in ILs. Thus far we have made a key advance on our understanding of these liquids near or below their glass transition temperature; where the internal motions slow to a regime that requires MAS to obtain high resolution NMR spectra.

Solid-State NMR Methods Development

My lab at its heart is technique driven. Thus, we are constantly working to apply NMR, particularly solid-state, in new and interesting ways to solve relevant problems in a variety of fields. In addition to work solely in my lab this includes projects led by my lab in collaboration with others, as well as applying our expertise in NMR to add value to projects led by others. We work with the latest fast spinning MAS probes and develop pulse sequences and rotor packing tool to make the most of this emerging technology.

All Publications 

https://www.ncbi.nlm.nih.gov/myncbi/andrew.nieuwkoop.1/bibliography/public/

Selected Publications 

  • Osborn Popp, T.M.;Karthikeyan, M.; Herman, E.M.;  Dufur, A.C.; Vetriani, C.;  Nieuwkoop, A.J.; Measurement of phospholipid lateral diffusion at high pressure by in situ magic-angle spinning NMR spectroscopy, Commun. Chem. 2025, https://doi.org/10.1038/s42004-025-01449-7)
  • Bernstein, A.D.; Asante, Ampadu, G.A.; Yang, Y.; Acharya, G.R.; Osborn Popp, T.M.; Nieuwkoop, A.J.; Effects of Ca2+ on the structure and dynamics of PIP3 in model membranes containing PC and PS, Biochem. 2024, (https://doi.org/10.1021/acs.biochem.4c00513)
  • Bichitra, B.; Acharya, G.R.; Grajeda, D.; Emerson, M.S; Harris, M.A.; Abeykoon, AM.M.; Sangoro, J.; Baker, G.A.; Nieuwkoop, A.J.; Margulis, C.J.; Do Ionic Liquids Slow Down in Stages?, J. Am. Chem. Soc. 2023,  (https://doi.org/10.1021/jacs.3c08639)
  • Osborn Popp, T.M.; Matchett, B.T.; Green, R.G.;Chhabra, I.;Mumudi, S.; Bernstein, A.D.; Perodeau, J.R.; Nieuwkoop, A.J.; 3D-Printable centrifugal devices for biomolecular solid state NMR rotors,  Mag. Res. 2023, 354, 107524. (https://doi.org/10.1016/j.jmr.2023.107524)
  • Perodeau, J.; Arbogast, L.W; Nieuwkoop A.J.;Solid-State NMR characterization of Lyopholized formulations of monoclonal antibody therapeutics,  Phamaceutics. 2023, 20(3), 1480-1489. (https://doi.org/10.1021/acs.molpharmaceut.2c00676)
  • Palmere, R.D.; Case, D.A.; Nieuwkoop, A.J; Simulations of Kindlin-2 PIP binding domains reveal protonation-dependent membrane binding modes. Biophys J.2021,120 (24), 5504-5512. (https://doi.org/10.1016/j.bpj.2021.11.021)
  • Friedrich, D.; Perodeau, J.; Nieuwkoop, A. J.; Oschkinat, H., MAS NMR detection of hydrogen bonds for protein secondary structure characterization. J. Biomol. NMR 2020, 74 (4-5), 247-256. (http://doi.org/10.1007/s10858-020-00307-z)
  • Retel, J. S., Nieuwkoop, A. J., Hiller, M., Higman, V. A., Barbet-Massin, E., Stanek, J., Andreas, L. B., Franks, W. T., VanRossum, B., Vinothkumar, K. R., Handel, L., Giuseppe-Palma, G., Bardiaux, B., Pintacuda, G., Emsley, L., Kühlbrandt, W., Oschkinat, H. “Structure of Outer Membrane Protein G in Lipid Bilayers” Nat. Comm. 2017 8(1), 2073. (http://doi.org/10.1038/s41467-017-02228-2)
  • Tuttle, M. D., Comellas, G., Nieuwkoop, A. J., Covell, D. J., Berthold, D. A., Kloepper, K. D., Courtney, J. M., Kim, J. K., Barclay, A. M., Kendall, A., Wan, W., Stubbs, G., Schwieters, C. D., Lee, V. M. Y., George, J. M. and Rienstra, C. M. "Solid-state NMR structure of a pathogenic fibril of full-length human alpha-synuclein" Nat. Struct. Mol. Biol. 2016 23(5), 409-15. (http://doi.org/10.1038/nsmb.3194)
  • Nieuwkoop, A. J., Franks, W. T., Rehbein, K., Diehl, A., Akbey, U., Engelke, F., Emsley, L., Pintacuda, G. and Oschkinat, H. "Sensitivity and resolution of proton detected spectra of a deuterated protein at 40 and 60 kHz magic-angle-spinning" J. Biomol. NMR. 2015 61(2), 161-71. (http://doi.org/10.1007/s10858-015-9904-0)
  • Barbet-Massin, E., Pell, A. J., Retel, J. S., Andreas, L. B., Jaudzems, K., Franks, W. T., Nieuwkoop, A. J., Hiller, M., Higman, V., Guerry, P., Bertarello, A., Knight, M. J., Felletti, M., Le Marchand, T., Kotelovica, S., Akopjana, I., Tars, K., Stoppini, M., Bellotti, V., Bolognesi, M., Ricagno, S., Chou, J. J., Griffin, R. G., Oschkinat, H., Lesage, A., Emsley, L., Herrmann, T. and Pintacuda, G. "Rapid proton-detected NMR assignment for proteins with fast magic angle spinning" J. Am. Chem. Soc. 2014 136(35), 12489-97. (http://doi.org/10.1021/ja507382j)
  • Anderson, T. M., Clay, M. C., Cioffi, A. G., Diaz, K. A., Hisao, G. S., Tuttle, M. D., Nieuwkoop, A. J., Comellas, G., Maryum, N., Wang, S., Uno, B. E., Wildeman, E. L., Gonen, T., Rienstra, C. M. and Burke, M. D. "Amphotericin forms an extramembranous and fungicidal sterol sponge" Nat. Chem. Biol. 2014 10(5), 400-6. (http://doi.org/10.1038/nchembio.1496)
  • Zhou, D. H., Nieuwkoop, A. J., Berthold, D. A., Comellas, G., Sperling, L. J., Tang, M., Shah, G. J., Brea, E. J., Lemkau, L. R. and Rienstra, C. M. "Solid-state NMR analysis of membrane proteins and protein aggregates by proton detected spectroscopy" J. Biomol. NMR. 2012 54(3), 291-305. (http://doi.org/10.1007/s10858-012-9672-z)
  • Nieuwkoop, A. J. and Rienstra, C. M. "Supramolecular protein structure determination by site-specific long-range intermolecular solid state NMR spectroscopy" J. Am. Chem. Soc. 2010 132(22), 7570-1. (http://doi.org/10.1021/ja100992y)
  • Nieuwkoop, A. J., Wylie, B. J., Franks, W. T., Shah, G. J. and Rienstra, C. M. "Atomic resolution protein structure determination by three-dimensional transferred echo double resonance solid-state nuclear magnetic resonance spectroscopy" J. Chem. Phys. 2009 131(9), 095101. (http://doi.org/10.1063/1.3211103)
  • Franks, W. T., Wylie, B. J., Schmidt, H. L., Nieuwkoop, A. J., Mayrhofer, R. M., Shah, G. J., Graesser, D. T. and Rienstra, C. M. "Dipole tensor-based atomic-resolution structure determination of a nanocrystalline protein by solid-state NMR" Proc. Natl. Acad. Sci. U. S. A. 2008 105(12), 4621-6. (http://doi.org/10.1073/pnas.0712393105)
  • Zhou, D. H., Shea, J. J., Nieuwkoop, A. J., Franks, W. T., Wylie, B. J., Mullen, C., Sandoz, D. and Rienstra, C. M. "Solid-state protein-structure determination with proton-detected triple-resonance 3D magic-angle-spinning NMR spectroscopy" Angew Chem Int Ed Engl. 2007 46(44), 8380-3. (http://doi.org/10.1002/anie.200702905)

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