Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

26-POS Board 26 FREE ENERGY SIMULATIONS OF ELECTROPORATION Gari Kasparyan 1 ; Jochen Hub 1 ; 1 Saarland University, Theoretical Physics, Saarbrücken, Germany

Biological cells are defined as the volume enclosed by a semi-permeable lipid membrane. Forming pores in those membranes plays a role in processes such as membrane fusion and fission, increasing the permeability of the membrane, and others. Electroporation is a method used for decades to help introduce drugs and genetic material in cells or generally as a pore forming modality. Although pores are heavily studied with a variety of methods, the free energy landscape of the initial stages of the pore formation is still not fully understood. We use molecular dynamics simulations to study the mechanisms and energetics of electroporation. We overcome the challenge of exploring the free energy landscape using umbrella sampling along a recently developed reaction coordinate[1, 2]. The potentials of mean force (PMFs) show that electric fields greatly stabilize open pores and lower the barrier for pore formation (as expected). An unexpected discovery is the way in which the pore formation energy barrier is influenced by the applied potential. As a result of that discrepancy between simulations and existing continuum models we propose a novel continuum model of electroporation. To verify our findings we compare two methods for establishing transmembrane potential in an MD simulation – external electric field and charge imbalance. [1] J. Hub and N. Awasthi, J. Chem. Theory Comput. 2017, 13, 2352- 2366[2] J. Hub, J. Chem. Theory Comput. 2021, 17, 1229−1239

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