A kinetic model for molecular diffusion through pores

Biochimica Et Biophysica Acta
Tommaso D'AgostinoMatteo Ceccarelli

Abstract

The number of pathogens developing multiple drug resistance is ever increasing. The impact on healthcare systems is huge and the need for novel antibiotics as well a new way to develop them is urgent, especially against Gram-negative bacteria. The first defense of these bacteria is the outer membrane, where unspecific protein channels (porins) modulate nutrients passive diffusion. Also polar antibiotics enter through this path and down-regulation and/or mutation of porins are very common in drug resistant strains. Our inability to come up with novel effective antibiotics mostly relies upon the insufficient comprehension of the key molecular features enabling better penetration through porins. Molecular dynamics simulations offer an extraordinary tool in the study of the dynamics of biological systems; however, one of the major drawbacks of this method is that its use is currently restricted to study time scales of the order of microsecond. Enhanced sampling methods like Metadynamics have been recently used to investigate the diffusion of antibiotics through bacterial porins. The main limitation is that dynamical properties cannot be estimated because of the different potential that the systems under study are experiencing. Rece...Continue Reading

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Citations

Apr 21, 2016·Biochimica Et Biophysica Acta·James C Gumbart, Sergei Noskov
Mar 4, 2017·The Journal of Physical Chemistry. B·Karunakar R PothulaUlrich Kleinekathöfer
Feb 6, 2017·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Mariano Andrea ScorciapinoMatteo Ceccarelli
Dec 4, 2019·Nature Reviews. Microbiology·Julia VergalliJean-Marie Pagès
Jul 25, 2018·ACS Infectious Diseases·Susruta SamantaMatteo Ceccarelli
Mar 19, 2019·Journal of Chemical Information and Modeling·Tomasz Pieńko, Joanna Trylska
Jun 16, 2016·Future Medicinal Chemistry·Mariano Andrea ScorciapinoMatteo Ceccarelli

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