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Protein systems spanning two membranes

Project 2MemProt
Research Area Bio Sciences
Principal Investigator(s) Prof.Dr. Ulrich Kleinekathöfer
Institution(s)
  • Jacobs University, Bremen, Germany
  • Universit√† degli Studi di Cagliari, Italy

Abstract

The study of membrane proteins embedded in their native environment, i.e., lipid bilayers and water is numerically still quite computer demanding and requires some effort especially when longer simulation times are needed. Extremely challenging are the simulations of protein complexes that span over two membranes. For example, gram-negative bacteria have an outer and an inner membrane and some efflux pump systems, the protein machineries responsible for the occurrence of multidrug resistance, do work across both membranes. Bacterial resistance against antibiotics is becoming a real threat in treating several diseases these days. The availability of the atomic structure of several efflux pumps or reliable models via homology opens the possibility to study the structure-function relationship computational via large-scale molecular dynamics (MD) simulations. A simulation of the whole complex incl. patches of the outer as well as the inner membrane is needed to understand the cooperative effects of the individual proteins. Some functions of the individual proteins are at least partially understood by now, but it is clear that the function of the pump needs the interplay of the individual proteins. The large size of the system and the complexity of the interaction among the different parts of the pump make the investigation challenging and very time-consuming as well.

The Italian as well as the German groups have experience in modelling the influx of ions and antibiotics through cell membranes and furthermore in studying parts of the efflux system. The function of one transporter involved in the efflux was recently studied in a joint effort. Now, the complete efflux system consisting of more than half a million atoms shall be attacked using the MD code NAMD developed by the Schulten group. This code has excellent parallel scaling properties making it an ideal tool for making use of the DEISA infrastructure in an European project which would be otherwise impossible.

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