Structural Membrane Proteomics

Structural Membrane Proteomics

Project Group of Department of Molecular Membrane Biology (MMB)

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The group in the department applies computational methods to investigate structure-functional relationships in selected membrane proteins. We study the dynamics and conformational changes in transmembrane proteins by means of several molecular mechanics and bioinformatics techniques. The close collaboration between crystallographers, biochemists and biophysicists allows us to combine experimental and theoretical results, leading to a better understanding of the mechanisms underlying the function of membrane proteins. In one project we investigate the coupled electron-proton transfer reactions in aerobic terminal oxidases, in particular the dynamics and conformational changes associated with electron and proton transfer. We are actively involved in a number of collaborative projects with experimental groups studying the transport mechanism and the regulation of activity of several secondary active transporters.

Theoretical studies on the proton translocation mechanism of cytochrome c oxidase from Paracoccus denitrificans and other terminal oxidases.

K-pathway of cytochrome c oxidase from Paracoccus denitrificans. Snapshot of molecular dynamics simulations showing part of the hydrogen-bonded network of the K-pathway.

Using continuum electrostatics and molecular dynamics calculations we study the titration behaviour of selected residues of Paracoccus denitrificans cytochrome c oxidase, the kinetics of protein movements coupled to proton and electron transfer, and the conformational fluctuations associated with these processes.

Computational studies of the mechanism of the Na+/H+ antiporter NhaA from Escherichia coli.

Clusters of strongly electrostatically interacting ionisable groups for NhaA antiporter structure. Zones of negative and positive potential are coloured red and blue, respectively. Four clusters of interacting residues at pH 4 are shown in grey, green, magenta and yellow.

The aim of this project is to understand the mechanism of ion transport and regulation of this protein, in particular the role of individual residues by combining continuum electrostatic calculations and long-range molecular dynamics simulations. The NhaA Na+/H+ antiporter is studied in close collaboration with the group of Prof. Etana Padan (Hebrew University of Jerusalem, Israel). Our results provided valuable information on the activation of the antiporter, on the role of individual amino acid residues, and provide a framework for the interpretation and design of further experimental work.

A homology model of the Na+/proline transporter PutP with functional implications

Another project deals with the Na+/proline transporter PutP. It focuses on structure prediction using homology modelling techniques. The identification of the substrate binding sites using docking calculations allowed us to get initial information about specific protein-ligand interactions. We aim to understand the structural changes coupled with the transport of the substrate across the membrane and the process leading to these structural changes. These studies are accompanied by the experimental work done by the group of Prof. Heinrich Jung (LMU, München).


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