Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Friday Speaker Abstracts

INSIGHT FROM ADVANCED MOLECULAR SIMULATION APPROACHES INTO TRANSPORT ACROSS BACTERIAL MEMBRANES Abhishek Acharya 1 ; Jigneshkumar D Prajapat 1 ; Ulrich Kleinekathöfer 1 ; 1 Jacobs University Bremen, Dept. of Physics and Earth Sciences, Bremen, Germany Channels in the outer membrane of Gram-negative bacteria provide essential pathways for the controlled and unidirectional transport of ions, nutrients and metabolites into the cell. At the same time the outer membrane serves as a physical barrier for the penetration of noxious substances such as antibiotics into the bacteria. In this presentation the simulation of ion and substrate transport across such bacterial channels will be detailed. As examples, the translocations of the antibiotics fosfomycin, ciprofloxacin and enrofloxacin have been computed recently [1-3] and will be briefly reviewed. Moreover, we investigated a variety of substrates and their free energy surfaces along the Pseudomonas aeruginosa outer membrane channel OprO using the well advanced metadynamics and umbrella sampling free energy methods. The free energy calculations have been performed to illustrate the difference of computed free energies by virtue of increasing the substrate complexity along with the involved asymmetry of the outer membrane channels during the substrate translocation process. Thus, the resulting comparative analysis helps us to choose the most appropriate method for future calculations of similar case studies.[1] J. D. Prajapati, U. Kleinekathöfer and M. Winterhalter, How to Enter a Bacterium: Bacterial Porins and the Permeation of Antibiotics, Chem. Rev. 121, 5158–5192 (2021).[2] A. Acharya, J. D. Prajapati and U. Kleinekathöfer, Improved Sampling and Free Energy Estimates for Antibiotic Permeation through Bacterial Porins, J. Chem. Theory Comput. 17, 4564–4577 (2021). [3] V. K. Golla, J. D. Prajapati and U. Kleinekathöfer, Millisecond- Long Simulations of Antibiotics Transport through Outer Membrane Channels, J. Chem. Theory Comput. 17, 549–559 (2021).

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