Mads Nygaard
I am a Post-graduate Fellow with MSc in Biochemistry in the field of protein chemistry. My degree in Biochemistry has given me a solid understanding of protein chemistry and structural biology. My Master Project provided me a solid knowledge of protein biophysics. The research was carried
out in Structural Biology and NMR Laboratory at the University of Copenhagen under the supervision of Prof. Birthe Kragelund, where I had the opportunity to get hands on experience with protein expression, and different spectroscopic methods including nuclear magnetic resonance (NMR) spectroscopy. The spectroscopic methods were complemented with all-atom molecular dynamics (MD) simulations and coarse-grained methods for sampling of intrinsically disordered proteins, such as Flexible Meccano.At CBL, I am working with enhanced sampling MD methods to study different intrinsically disordered domains of key players in autophagy and cell proliferation. We aim at accurately samples their conformations in the computer and be able to describe the effects induced upon post-translational modifications (PTMs), binding with folded proteins or cancer-related mutations. The nature of intrinsically disordered proteins makes them challenging to study with conventional methods developed for folded proteins. We are thus testing new physical models for disordered proteins and integrate our data with experimental data from NMR.
I also recently started to focus on structural investigations of transcription factors in complex with DNA and the effects induced upon protonation of histidine.
We are developing our own pipelines in Python to automatize the preparation of the proteins for simulations and the post-processing of the MD trajectories with the ambition to use these techniques for high-throughput screening of effects of PTMs and mutations. I am also developing Python-based tools to back-calculate from the MD ensembles NMR parameters such as chemical shifts, NOEs, the radius of hydration and to measure the agreement between the calculated and experimental properties in folded and unfolded proteins.
Publications at CBL:
(1) equal first co-authorship
Nygaard M, Kragelund BB, Papaleo E, Lindorff-Larsen K. An efficient method for estimating the hydrodynamic radius of disordered protein conformations. Biophys J, 2017, 113: 550-557.
Nygaard M(1), Terkelsen T(1), Vidas Olsen A, Sora V, Rizza F, Salamanca Viloria J, Bergstrand S, Di Marco M, Vistesen M, Tiberti M, Lambrughi M, Jaattela M, Kallunki T, Papaleo E*. The mutational landscape of the oncogenic MZF1 SCAN domain in cancer. Front in Mol Biosci (Nature publishing group), 2016, 3:78.
Oskarsson KR, Nygaard M, Ellertsson BO, Thorbjarnardottir SH, Papaleo E*, Kristjansson MM*. A single mutation Gln142Lys doubles the catalytic activity of VPR, a cold-adapted subtilisin-like serine proteinase. BBA Prot. Proteomics, 2016, 1864: 1436-43.
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