Ulrich Zachariae Group

Computational Biophysics and Drug Discovery

Divisions of Computational Biology & Physics, University of Dundee


February 2019 - Interaction of antibiotics with PorB channels from Neisseria meningitidis

Our collaborative work with Claudia Steinem's group from Göttingen shows how the beta-lactam ampicillin binds to PorB from N. meningitidis or meningococca, the causative agent of bacterial meningitis, with many important implications for antibiotic design. The study is now out in Scientific Reports.

July 2018 - Functional basis for potassium channel ion selectivity revealed

Our work showing why potassium channels are so selective for the conduction of only K+ ions has just been published in Nature Chemistry. See also the News & Views article by Ben Corry in the same issue.

May 2018 - Giulia has passed her viva!

Congratulations to Giulia who has just passed her PhD viva! Really well done and a great viva talk too.

March 2018 - Structure and Dynamics of an Intellectual Disability Causing Mutation of O-GlcNAc Transferase Resolved

Salomé's work in collaboration with Daan van Aalten's group shows the importance of addressing questions of medical relevance by a multidisciplinary approach, as published in Cell Chemical Biology. See also press reports in, e.g., Drug Discovery Today .

March 2018 - Minireview Published on "Ten Years of High Resolution Structural Research on the Voltage Dependent Anion Channel (VDAC)"

We summarise recent developments and the present status of the field of VDAC structure and dynamics in a review in Front. Physiol.

January 2018 - Owen's Work on the Transfer of Sodium Ions in GPCRs published

The potential importance of the intracellular movement of sodium ions across GPCRs is shown in the journal Structure.

December 2017 - Results on efflux pump conduit published in Scientific Reports

Giulia's experimental and computational work on the regulation of the efflux duct MtrE have now been published online in Scientific Reports.

May 2017 - Results on efflux pump published in Nature Microbiology

The results our Postdoc Salomé obtained on the ABC-driven efflux pump MacAB-TolC from E. coli in a collaboration with Ben Luisi and Dijun Du from the Cambridge University have now been published in the journal Nature Microbiology. See also Press release.

February 2017 - Alex Krah's paper on MATE drug efflux transporters is online

Alex's work on the functional mechanism of NorM from Vibrio cholerae is now available as manuscript in press.

October 2016 - Owen's review on GPCR voltage-regulation published

Owen's review on the importance of voltage-sensing in G-protein coupled receptors for the drug discovery process has been published in Current Opinion in Pharmacology.

May 2016 - Paper on GPCR voltage-sensitivity published

Owen's and Giulia's paper in Structure, in which a mechanistic model for voltage sensing in class A GPCRs is presented, is now available online here.

Older News

Research Focus

Molecular Simulations of Membrane Protein Function

Proteins are the machinery of biological cells. To perform their duties, they must undergo conformational changes, much like the motions of macroscopic machines. These dynamics can be followed and studied by molecular dynamics simulations, which allow us to gain insight into the mechanisms by which they work, and into the underlying physical principles, for instance the governing energetics.

We apply and develop simulation methods on a range of length and time scales, with a particular focus on membrane proteins, membranes 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 Computational Electrophysiology (shown above), which allows the prediction of channel ion conductance and selectivity based on electrochemical gradients, along with elucidating the mechanism of permeation. Of special interest to us are, for example, 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). We also investigate the molecular basis for the impressive elasticity of tandem repeat proteins, such as importin-beta and CRM1. CRM1 is the major cellular exporter of proteins from the cell nucleus and plays a very important role in cancer progression. We also look at protein-membrane interactions using coarse-grained models and we have recently developed a method to accurately quantify pattern formation in membranes and other mixed systems.

Join Us

Several PhD studentships in the area of computational biophysics and molecular modelling & simulations are available in the groups of Dr Ulrich Zachariae and Dr Andrei Pisliakov at the University of Dundee. The positions are fully funded through the EPSRC and BBSRC PhD programmes. The interdisciplinary projects will focus on biomolecular simulations (molecular dynamics, QM/MM, etc) of various proteins involved in fundamental biological processes. For more info, see Jobs and follow the links there. Also have a look at our recent publications.

We are looking for biochemists, chemists, biologists and physicists interested in working at the interface between the traditional disciplines. Contact us if you are interested in studying the mechanisms that drive biology with a view to developing drugs - and if you like computational work. For a clearer picture, read more about our present research and have a look at our publications.