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Updated: Jan 26, 2026

Preparation of High-Temperature Sample Grids for Cryo-EM
Published on: July 26, 2021
Biophysical Characterization of a Nanodisc with and without BAX: An Integrative Study Using Molecular Dynamics
Cesar A López1, Mark F Swift2, Xiao-Ping Xu2
1Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA; Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos NM 87545, USA.
Abstract:
B cell lymphoma-2-associated X protein (BAX) plays a pivotal role in triggering cell apoptosis by permeabilizing the mitochondrial outer membrane. Contrary to previous findings, recent electron microscopy (EM) experiments showed that BAX monomers are able to perturb phospholipid nanodiscs (NDs) by forming lipidic pores. Here, we provide structural and thermodynamic interpretation of such data using multiscale resolution molecular dynamics (MD) simulations. Our results suggest that BAX is able to disrupt the stability, lateral packing and enhance the desorption propensity of the lipids in the ND, resulting in the formation of a stable toroidal-like pore. These findings prompted to re-evaluate the previously reported cryo-EM data to generate an improved reconstruction, thereby allowing for a more accurate localization of BAX in the EM map. We conclude that the reduced stability of the BAX-embedded ND eliminates the necessity of forming active BAX oligomers for its disruption.
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