What question did this study set out to answer?

To quantify the permeability of metabolites across the bacterial microcompartment shell using molecular dynamics simulation.

February 21, 2026

BPS2026 – Molecular modeling and molecular dynamics simulation of a packed and intact bacterial microcompartment

Key Points

To quantify the permeability of metabolites across the bacterial microcompartment shell using molecular dynamics simulation.
Utilized classical molecular dynamics simulation to model the permeability of G3P and DHAP through the BMC shell.
Conducted simulations using the Haliangium ochraceum model (PDB: 6MZX) with approximately 10 million atoms.
Managed large datasets and challenges associated with high-scale molecular simulations.
Identified multiple permeation events for G3P and DHAP across the BMC shell over 750 ns of simulation.
Permeability coefficients for G3P and DHAP were found to be very high and similar, with significant concentration gradients maintained.
Estimated viscosity within the packed BMC shell is at least ten-fold higher than in neat solution, affecting permeability estimates.

Abstract

Bacterial microcompartments (BMCs) are protein-bound organelles found in some bacteria which encapsulate enzymes for enhanced catalytic activity. These compartments spatially sequester enzymes within semi-permeable shell proteins, and are packed full of enzyme cargoes and metabolites. Coupling recent SAXS and proteomics work, it is possible to develop molecular models for these microcompartments and interrogate enzyme and metabolite dynamics within. This study primarily quantifies the permeability of metabolite Glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP) across the BMC shell through classical molecular dynamics simulation. The Haliangium ochraceum model of BMC shell (PDB: 6MZX) was used to model an intact BMC of approximately 10 million atoms. Working at this scale presented its own challenges in managing large datasets, with multiple challenges and hardware advances discussed that facilitated this work. Over approximately 750 ns of aggregate simulation, we see multiple permeation events for these metabolites that were added at high concentration through the pores present within BMC shell tiles. When compared to independent permeability estimates for the same metabolites determined through replica exchange umbrella sampling simulations, the permeabilities varied by approximately three orders of magnitude. The permeability coefficients for both G3P and DHAP are highly similar and very high, such that only very small concentration gradients can be maintained across the BMC shell between the cytosol and BMC interior. The large simulation systems also facilitated comparisons for molecular diffusivity in the crowded environment within the BMC shell. By our estimates, the viscosity within a packed BMC shell is at least ten-fold higher than it would be in neat solution, and is the real driver for varying permeability estimates we obtain through simulation. These findings will be used as design inputs for future bioengineering efforts to make products from BMCs.

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