title: Microscopic Mechanism of Antibiotics Translocation through a Porin.
abstract: OmpF from the outer membrane of Escherichia coli is a general porin considered to be the main pathway for beta-lactam antibiotics. The availability of a high-resolution crystal structure of OmpF and new experimental techniques at the single-molecule level have opened the way to the investigation of the microscopic mechanisms that allow the passage of antibiotics through bacterial pores. We applied molecular dynamics simulations to investigate the translocation process of ampicillin (Amp) through OmpF. Using a recent algorithm capable of accelerating molecular dynamics simulations we have been able to obtain a reaction path for the translocation of Amp through OmpF. The mechanism of passage depends both on the internal degrees of freedom of Amp and on interactions of Amp with OmpF. Understanding this mechanism would help us design more efficient antibiotics and shed light on nature's way of devising channels able to enhance the transport of molecules through membranes.
authors.affiliation: Computational Science, Department of Chemistry and Applied Biosciences, ETH Zurich, USI Campus, Lugano, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ceccarelli
authors.forename: Christophe
authors.initials: C
authors.lastname: Danelon
authors.forename: Alessandro
authors.initials: A
authors.lastname: Laio
authors.forename: Michele
authors.initials: M
authors.lastname: Parrinello
mesh_terms: D000465:Algorithms; D000667:Ampicillin / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001692:Biological Transport; D003198:Computer Simulation; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D018272:Porins / Q000378:metabolism*; D047090:beta-Lactams / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C109237:OmpF protein; D018272:Porins; D047090:beta-Lactams; D000667:Ampicillin