Soroosh Pezeshki

• The outer membrane porins F and C (OmpF and OmpC) are major pores in the cell membrane of the Gram-negative bacterium Escherichia coli. They are considered the main pathways for ions and molecules through the membrane. Using the crystal structures, it is possible to study OmpF and OmpC in computer simulations. In this thesis, the ion conductance through these nano pores is simulated in all-atom molecular dynamics. Although the amino acid sequences of both pores are similar, their conductance is different. The temperature dependence of the conductance is calculated for different salt concentrations. Good agreement is seen in the comparison between simulations and experiments. The advantage of molecular dynamics simulations is that they allow a deeper view on the molecular interaction leading to the macroscopic observation. Ion pathways can be followed, and the interaction of ions with certain residues can be observed. Both pores, OmpF and OmpC, have a charged constricted area in the middle of the pore. The behavior of the pore can be changed by mutating key residues in this constriction zone. The effect of mutations on the transport of ions is investigated and compared to the results obtained from wild type OmpF. Also here, experimental measurements show good agreement with the simulations. Furthermore, porins are the main pathways of antibiotics into the cell. The translocation of antibiotics through membrane is not yet understood in all details. During translocation, a blocking of pores through antibiotics is observed. Here, blocking of porins by the beta lactam antibiotic ampicillin is simulated, as well as, translocation of ampicillin through OmpF.