10.1021/acsinfecdis.8b00149.s001 Susruta Samanta Susruta Samanta Igor Bodrenko Igor Bodrenko Silvia Acosta-Gutiérrez Silvia Acosta-Gutiérrez Tommaso D’Agostino Tommaso D’Agostino Monisha Pathania Monisha Pathania Ishan Ghai Ishan Ghai Christian Schleberger Christian Schleberger Dirk Bumann Dirk Bumann Richard Wagner Richard Wagner Mathias Winterhalter Mathias Winterhalter Bert van den Berg Bert van den Berg Matteo Ceccarelli Matteo Ceccarelli Getting Drugs through Small Pores: Exploiting the Porins Pathway in <i>Pseudomonas aeruginosa</i> American Chemical Society 2018 antibiotic bacteria ceftazidime OccK 8 pore Pseudomonas aeruginosa substrate translocation Outer membrane proteomics 2018-07-24 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Getting_Drugs_through_Small_Pores_Exploiting_the_Porins_Pathway_in_i_Pseudomonas_aeruginosa_i_/6946055 Understanding molecular properties of outer membrane channels of Gram-negative bacteria is of fundamental significance as they are the entry point of polar antibiotics into bacteria. Outer membrane proteomics revealed OccK8 (OprE) to be among the five most expressed substrate specific channels of the clinically important <i>Pseudomonas aeruginosa</i>. The high-resolution X-ray structure and electrophysiology highlighted a very narrow pore. However, experimental <i>in vitro</i> methods showed the transport of natural amino acids and antibiotics, among them ceftazidime. We used molecular dynamics simulations to reveal the importance of the physicochemical properties of ceftazidime in modulating the translocation through OccK8, proposing a structure–function relationship. As in general porins, the internal electric field favors the translocation of polar molecules by gainful energy compensation in the central constriction region. Importantly, the comparatively narrow OccK8 pore can undergo a substrate-induced expansion to accommodate relatively large-sized substrates.