Professor Ulrich Zachariae
Computational Biology, School of Life Sciences
Dr Ulrich Zachariae obtained his PhD in the structural biophysics lab of Wolfgang Baumeister at the Max Planck Institute for Biochemistry in Munich (2004).
Between 2005 and 2010, he worked as a Postdoc with Helmut Grubmüller and Bert de Groot at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, and as a drug researcher for AstraZeneca in Alderley Park, focusing on computational and theoretical biophysics. From 2011—2013, Ulrich was an independent SUPA Advanced Fellow at the School of Physics at the University of Edinburgh, building up a team of researchers interested in membrane-protein simulations. He joined the University of Dundee as Reader in Physics and Life Sciences in May 2013.
- Membrane biophysics
- Ion channels: Gating mechanisms, permeation and selectivity
- Design of new antibacterial compounds
- Flexible protein scaffolds investigated by atomistic simulations with close links to experiments.
Atomistic & Coarse-Grained Simulations of Proteins and Membranes
Proteins form the machinery of biological cells. To perform their actions, they must undergo conformational changes, much like the motions of macroscopic machines. These can be followed and studied by molecular dynamics simulations, which allow us to gain insight into the mechanisms by which they work - and the underlying energetic principles.
We apply and develop simulation methods on a range of length and time scales, especially focusing on membrane proteins and ion channels. Membrane-bound proteins form a large part of the proteome and control many of the cell's fundamental functions. To investigate ion channels, we have developed CompEl, "computational electrophysiology", which allows the prediction of channel ion conductance and selectivity based on electrochemical gradients. Of special interest to us are potassium channels, membrane pores formed by antimicrobial peptides (e.g., dermcidin), and pores in the outer membrane of bacteria that are found to be mutated in strains resistant to antibiotics (e.g., Neisserial PorB).
Movies of ion conduction across KcsA (first video) and dermcidin (second video) are shown below. In KcsA, potassium ions are shown as purple and pink spheres, while the protein is shown in green and water in red and white. In the second movie on dermcidin, the peptide aggregate is coloured blue and orange, and chloride ions are shown in red. The grey spheres depict lipid membrane head groups. We also investigate the molecular basis for the impressive elasticity of solenoid proteins, such as importin-beta and CRM1, and we have developed methods to quantify pattern formation in many-particle systems.
Clues to the mechanism of yeast infections, which present risks to both humans and crops, have been identified.
Vacuum cleaners that unblock brain vessels, super normal design for extraordinary bodies, and the ways in which our medical data can aid the COVID-19 fight are just some of the topics to be explored at the University of Dundee next week.
The mechanism of a protein which transports ammonium across cell membranes has been discovered in research led at the University of Strathclyde, in collaboration with the University of Dundee and the Université Libre de Bruxelles.
Computational Biophysics and Drug Discovery