|Research Area||Bio Sciences|
|Principal Investigator(s)||Prof.Dr. Ulrich Kleinekathöfer|
Keeping the upper hand with bacterial resistance against antibiotics will require that Information at molecular level should be available form different techniques, and computational simulations can play an important role thereon. One of the resistance mechanisms implies the overexpression of the efflux pumps, very complex systems involved in the extrusion of different substrates (and also antibiotics and other drugs) from the bacteria. The efflux systems we are interested in belong to the RND family and are responsible for the transport of substrates through the inner as well as the outer membrane of gram-negative bacteria. Since the atomic structure of several efflux pumps were resolved recently or reliable models have been assembled via homology, one now has the possibility to study the structure-function relationship computational via large-scale molecular dynamics (MD) simulations. Both the Italian and the German groups have experience in modelling the influx of ions and antibiotics through cell membranes and now join forces and experience to tackle the more complex problem of efflux pumps. Because of this the system of study consists of several hundred thousand atoms. The MD code NAMD developed by the Schulten group which has excellent parallel scaling properties will be used on the DEISA infrastructure to study these very large systems in an European project which would be otherwise impossible. Studying molecular details of the efflux of different antibiotics in different bacteria, such as E.Coli and P.Aeruginosa, will help to understand why antibiotics are pumped out of the bacterial cell and therefore are unable to fulfil there task of destroying the cell.