Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

50-POS Board 50 MULTIBILLION ATOM MOLECULAR DYNAMICS SIMULATIONS OF COMPLEX CELLULAR MEMBRANES Noah Trebesch 1,2 ; Emad Tajkhorshid 1,2,3 ; 1 University of Illinois at Urbana-Champaign, Center for Biophysics and Quantitative Biology, Urbana, IL, USA 2 University of Illinois at Urbana-Champaign, Beckman Institute for Advanced Science and Technology, Urbana, IL, USA 3 University of Illinois at Urbana-Champaign, Department of Biochemistry, Urbana, IL, USA Membranes are the basic organizational and defensive unit of the cell, and they thus play a vital role in biological function. Electron microscopy (EM) can provide 3D structures of these membranes, and, with the advent of exascale computing, there is a new opportunity to use molecular dynamics (MD) simulations to elucidate the intricate biophysical connection between the complex composition, structure, and function of these membranes. To take advantage of this opportunity, we have developed xMAS (Experimentally-Derived Membranes of Arbitrary Shape) Builder, software designed to turn EM structures and experimentally-derived lipid and protein compositions of cellular membranes into atomistic models that are suitable for MD. xMAS Builder generates these models using a series of custom-designed modeling steps, including simulating Lennard-Jones particles while attracted to grid-based potentials to optimize the packing of the membrane lipids, fixing ring piercings and other complex lipid clashes using a newly developed energy minimization technique, and utilizing grid-based potentials to equilibrate the models while maintaining their experimentally-derived shapes. Using xMAS Builder, we have built the first cell- scale (~4.5 billion atom, ~1.9μm³) model of a representative cellular membrane (a helicoidal system from the endoplasmic reticulum called a Terasaki ramp), and we have also built several models of a smaller synthetic system with equivalent complexity. Preliminary simulations of these models have demonstrated their potential to reveal fundamental insights into the general behavior of cellular membranes, including the principles that determine the number of lipid molecules that can be accommodated by curved membranes and the natural response of cellular membranes to perturbations to their structures. These preliminary results support the expectation that xMAS Builder will soon enable MD simulations that leverage exascale computing to provide compelling insight into the complex molecular basis of cellular membrane structure and biological function.

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