Molecular Modeling and Molecular Dynamics Simulation of a Packed and Intact Bacterial Microcompartment

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biology

Background:

• Bacterial microcompartments (BMCs) are protein-bound organelles that enhance enzymatic reactions by sequestering enzymes and metabolites.
• Understanding metabolite transport across BMC shells is crucial for their function and bioengineering applications.

Purpose of the Study:

• To quantify the permeability of glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP) across the BMC shell.
• To investigate the influence of the crowded BMC interior on molecular diffusion and viscosity.

Main Methods:

• Classical molecular dynamics simulations of a large-scale bacterial microcompartment model (PDB: 6MZX) from *Haliangium ochraceum*.
• Replica exchange umbrella sampling simulations to determine independent permeability estimates.
• Analysis of molecular diffusivity and viscosity within the simulated BMC environment.

Main Results:

• Multiple permeation events of G3P and DHAP were observed through BMC shell pores during simulations.
• Permeability coefficients for G3P and DHAP were found to be very high and similar, allowing only small concentration gradients.
• Internal viscosity within the packed BMC shell was estimated to be at least 10-fold higher than in solution.

Conclusions:

• BMC shells exhibit high permeability to key metabolites G3P and DHAP.
• The high internal viscosity of BMCs significantly affects molecular diffusion and likely contributes to observed permeability variations.
• These findings provide critical design parameters for future bioengineering efforts utilizing BMCs.