Simulating transport properties through bacterial channels

Gram-negative bacteria have several porins in their outer membrane: they act as gates in the exchange of molecules and are also considered the main pathway for antibiotics. Bacteria are able to resist the action of antibiotics simply by closing off physical access to their interior, either underexpressing porins or decreasing the porin's internal size. The dissemination of pathogens resistant to common antibiotics requires the development of new classes of drugs with improved properties. Understanding how compounds diffuse through bacterial porins can aid in the design of new antibiotics with better penetration power, partially solving one of the main problem of resistance. The diffusion of antibiotics through porins is a molecular-based process, controlled mainly by electrostatic interactions, as has been shown experimentally. Data from single molecule experiments are available in the literature but provide only indirect evidence of the transport. Molecular dynamics simulations at the molecular scale, combined with a recent algorithm able to extend simulations to biologically interesting times, have been shown to complement experiments, providing detailed information on the transport of antibiotics through porins.