Community Research and Development Information Service - CORDIS



Project ID: 276920
Funded under: FP7-PEOPLE
Country: Germany

Biophysical modelling of cell membrane transport

The physiology of living cells depends on the proteins that take molecules across membranes. Computer modelling has helped to elucidate the structure and function of these transport proteins in health and disease.
Biophysical modelling of cell membrane transport
The EU-funded BIOL-TRANSP-COMPUT (Mechanisms of transport across biological membranes) project has investigated the whole complex of membrane protein functions. Researchers selected three proteins for this study: SecA motor protein, AHA2 plasma membrane proton pump and the light-sensitive cation channel. The goal was to uncover details of chemo-mechanical coupling and protonation dynamics in mediating transport using computational analysis.

The basis of the BIOL-TRANSP-COMPUT research centred on hydrogen bonding. Protonation is the addition of a hydrogen ion or proton to a substance, thereby making it more acidic. This process of hydrogen bonding is critical in proton transfer systems and protein conformations that enable the transport of molecules across cell membranes.

SecA uses adenosine triphosphate (ATP)-dependent chemo-mechanical coupling to translocate proteins across membranes in bacteria. Bioinformatics and sequence analyses along with SecA dynamics computations provided novel insight in this area. An all-atom simulation in bulk water provided valuable insights into conformational dynamics of SecA. Important observations included the tight coupling of protein and water interactions with the nucleotide-binding state.

The AHA2 plasma membrane proton pump belongs to the P-type ATPases family. These complex enzymes act as secondary transport systems by using long-distance conformational coupling. Analysis by the project demonstrated the access to the water of the primary proton donor/acceptor group and interconnection of the structure and dynamics with the protonation state.

Channelrhodopsins are light-sensitive retinal transporter proteins. Researchers obtained structural information about channelrhodopsin variants by sequence analyses and derived subsequent homology models. The reaction cycles of retinal proteins are initiated by the photoisomerisation of the retinal chromophore. Application of combined quantum mechanics/molecular mechanics analysis has shown that the molecular dynamics in the rhodopsins is shaped by hydrogen bonds with surrounding protein and water groups.

Hydrogen bond dynamics is essential for the conformation of transporters. General knowledge of groups that may store protons is necessary to understand the mechanism of action of proton-coupled biological systems. The outcomes of this project could therefore have significant impact on drug design in biomedical research.

Related information


Biophysical modelling, transport protein, SecA, AHA2, channelrhodopsin
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