All-Atom Molecular Dynamics Simulations of Bacterial Porins Phoe from E. Coli And VCA1008 from V. Cholerae: Revealing the Molecular Origin of Ion Selectivity

Outer membrane pore-forming proteins play an essential role in survival, adaptation and response to environment of Gram-negative bacteria, and contribute for invasion of host organisms and even for drug resistance of such pathogens. These membrane proteins form large and almost unspecific ion channels through the membrane and a lot of effort was made to determine and to justify the ion selectivity of these pores (Alcaraz et al. 2009). Altough there is some sequence and structural similarities between porins PhoE from E. coli and VCA1008 from V. cholerae (Goulart et al. 2009) their selectivities for different inorganic ions seem to be quite different. On the other hand, molecular dynamics simulation of large systems are now reliable and should give detailed atomic information about ion dynamics though the channel, charge distribution and specific interacting site. Molecular dynamics simulations of the related porins OmpC and OmpF from E. coli, were recently presented and some of these aspects were explored (Biro et al. 2010). We have built up two systems, one for PhoE (PDB ID: 1PHO) and another one for VCA1008 (constructed by comparative modeling, Goulart et al. 2009), consisting of the channel trimer embedded in a DPPC lipid bilayer. A constant electrical field will be applied for different ionic concentrations of LiCl, NaCl, KCl and CaCl2. The conductance, charge distribution and the identification of binding sites for each condition should be compared with experimental results. The elucidation of the charge-controlled mechanism inside the channels could emerge from our approach.[1] Alcaraz et al., Biophysical J. 96 (2009) 56-66.[2] Biro et al., Biophysical J. 98 (2010) 1-10.[3] Goulart et al., FEMS Microbiol Lett 298 (2009) 241-248.