Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

1-POS Board 1 COMPREHENSIVE EXPLORATION OF FLUROQUINOLONE PERMEATION PATHWAYS THROUGH THE BACTERIAL OMPF CHANNEL Abhishek Acharya ; Jigneshkumar D Prajapati 1 ; Ulrich Kleinekathöfer 1 ; 1 Jacobs University Bremen, Department of Physics and Earth Sciences, Bremen, Germany Several antibiotics cross the outer membrane of Gram-negative bacterial cells using diffusion channels called porins. While a host of experimental and simulation studies have provided useful insights into the general mechanism of permeation, this is limited to a few antibiotics. Moreover, a quantitative comparison of permeation mechanisms for different antibiotics is needed for a better understanding of how variations in antibiotic and channels affect the permeation rates. Previously, we described how temperature accelerated sliced sampling (TASS) can be employed for an improved estimation of free energies for antibiotic permeation [1]. Here, we employ the TASS scheme for investigating and comparing the permeation mechanism of two fluroquinolone antibiotics – ciprofloxacin and enrofloxacin - through the Escherichia coli OmpF channel to better understand how a slight modification in an antibiotic influences the respective permeation paths through the channel. Our simulations results support previously reported experimental observations of a slower permeation rate and significantly longer dwell time for enrofloxacin. This is attributable to differences in the permeation paths accessible to the two antibiotics because of terminal different amino groups.

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