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Titolo: Molecular simulations reveal the mechanism and the determinants for ampicillin translocation through OmpF
Autori: 
Data di pubblicazione: 2010
Rivista: 
JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL  
Abstract: We use a multiscale approach, combining molecular dynamics simulations with metadynamics, to simulate the translocation of ampicillin through OmpF from Escherichia coli (E. coli). In-depth analysis has allowed us to reveal the complete picture of the translocation process in terms of both energetics and physicochemical properties. We have demonstrated the existence of a unique affinity site at the constriction region, accessible from both sides and defined by specific pore-antibiotic interactions. By providing optimal binding, the constriction region works like an enzyme toward the permeation of ampicillin. We find reduction in entropy to be compensated by enthalpic contributions from a favorable network of interactions (hydrogen bonds and hydrophobic contacts) which is also mediated by two slow water molecules bridging the antibiotic pore interactions. Finally, as ampicillin assumes a preferential value for a torsional angle when at the constriction region, we investigated the consequence of the conformational preorganization of ampicillin toward its translocation. As a whole, our analysis opens the way to chemical modifications of antibiotics to allow improving uptake through porins contributing to combat bacterial resistance.
Handle: http://hdl.handle.net/11584/108927
Tipologia:1.1 Articolo in rivista

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