Investigating the Bromoform Membrane Interactions Using Atomistic Simulations and Machine Learning: Implications for...

Methane emissions from livestock contribute to global warming. Seaweeds used as food additive offer a promising emission mitigation strategy because seaweeds are enriched in bromoform─a methanogenesis inhibitor. Therefore, understanding bromoform storage and production in seaweeds and particularly in a cell-like environment is crucial. As a first step toward this aim, we present an atomistic description of bromoform dynamics, diffusion, and aggregation in the presence of lipid membranes. Using all-atom molecular dynamics simulations with customized CHARMM-formatted bromoform force field files, we investigate the interactions of bromoform and lipid bilayer across various concentrations. Bromoform penetrates membranes and at high concentrations forms aggregates outside the membrane without affecting membrane thickness or lipid tail order. Aggregates outside the membrane influence the membrane curvature. Within the membrane, bromoform preferentially localizes in the membrane hydrophobic core and diffuses the slowest along the membrane normal. Employing general local-atomic descriptors and unsupervised machine learning, we demonstrate the similarity of bromoform local structures between the liquid and aggregated forms.