February 2022 - New findings identify clues to the mechanism of yeast infections

The results from Giulia's biomolecular simulations explain experimental observations made by our long-standing collaborators Arnaud Javelle and Anna-Maria Marini to yield key insights into the variations of substrate specificity and the type of mechanism for transporting ammonium in Mep-Amt-Rh proteins. Importantly, only one of these, Mep2, is capable of triggering filamentation in yeast, leading to infection. The findings have been published in mBio.

September 2021 - Welcome to new PhD students!

We are happy to announce that two new BBSRC-Eastbio funded PhD students have just joined the group, Alp Tegin Şahin and Tim Spankie - welcome to Scotland!

August 2021 - Our review on the current scientific discussion about potassium channel permeation mechanisms is out

Together with Wojciech, Bert and Andrei we summarise the current consensus - and disagreements - on the permeation mechanism at play in K+ channels underpinning their high permeation efficiency and strict ion selectivity in J. Mol. Biol. We review recent and older experimental and computational findings that may contribute to solving this problem, eventually!

July 2020 - Novel mechanism of selective NH4+ transport across the membrane published in eLife

Giulia's and Marcus' simulations, together with experimental results from our collaborators Arnaud Javelle and Paul Hoskisson (University of Strathclyde) and Anna-Maria Marini (Free University of Brussels), have revealed a novel "two-lane" mechanism of ammonium transport in bacterial and eukaryotic ammonium transporter, now published in eLife. Also see the insightful commentary article by William Allen & Ian Collinson on the significance of the findings.

October 2019 - Changes in the biomechanical properties of disease-related OGT mutants discovered

Salomé's work on mutations in the TPR domain of OGlcNac Transferase that are linked to Intellectual Disease shows that they change the dynamics and elasticity of the domain, with important implications for its ability to bind substrates. You can read the full story open access here:

August 2019 - Welcome to new PhD students

We are welcoming Dominik Gurvič and Callum Ives, who will join the group in early September and work alongside BBSRC-Eastbio PhD student Neil Thomson on MRC-funded PhD projects in the fields of ion channels and antibacterial resistance.

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.

Older News Items

Research Focus

Molecular Simulations of Membrane Protein Function

Biological cells enable the processes of life to occur within small, highly controlled compartments far from equilibrium. Cells are bounded by biomembranes, which are impermeable to many solutes and present a barrier to the exchange of matter and information between the outside and the inside of the cell. Since life requires a constant flux of matter and energy, specialized proteins have evolved that enable the transfer of ions, molecules, and signals between the cell and the external world. These processes are of such central importance for the life of cells that, in humans, about one-third of the genome encodes membrane proteins and almost one-half of all marketed drugs target membrane proteins.

A core interest of the group are the molecular mechanisms of membrane protein function, their interaction with drugs and substrates, and their wider environment inside lipid bilayers. Key present examples are membrane ion channels (e.g. the ion conduction efficiency and selectivity of potassium channels), pores in the outer membrane of bacteria that are found to be mutated in bacterial strains resistant to antibiotics (e.g., neisserial PorB), membrane surface receptors such as G-protein coupled receptors (e.g. muscarinic and opioid receptors), and membrane transporters such as multidrug efflux pumps or AmtB. Often, we are especially interested in the role of realistic membrane potentials in the function of these proteins.

Biomechanics of Tandem Repeat Proteins

Proteins form the machinery of biological cells. A large proportion of the proteome in higher organisms consists of solenoid repeat proteins, in which small conserved structural units stack to yield extended structures with large water-exposed surfaces. These proteins often play a role in enabling tight protein-protein binding interactions or they can serve as structural scaffolds. Depending on the fundamental repeating unit, they can be classified as HEAT, leucine-rich, tetratricopeptide, ankyrin or armadillo repeat proteins. In alpha-helical solenoid proteins, the building blocks usually consist of two to three alpha-helices. Alpha-solenoids such as HEAT repeat proteins are often exceptionally flexible and elastic, features that are key to their biological functions. In recent years, we have focused on tetratricopeptide (TPR) domains (shown here), studying their biomechanics and the role of changes in TPR dynamics in human disease.

Join the Team

Several PhD studentships in the area of computational biophysics, molecular modelling and simulations as well as chemoinformatics/machine learning are available in the group. The positions are fully funded through MRC, BBSRC and Wellcome Trust PhD programmes. For more information, see Jobs and follow the link there.

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 past and present research and have a look at our publications.

Further Information:

UZ Group Twitter profile.

Google Scholar profile (PI).

Contact Information.