Assembly and Analysis of Cell-Scale Membrane Envelopes.

Area of Science:

• Computational Biology and Biophysics
• Molecular Dynamics Simulations
• Cellular Modeling

Background:

• Exascale computing advances enable larger molecular simulations, approaching cellular scales.
• Current methods for constructing large biological structures for simulation are limited.
• Developing tools for cell-scale modeling is crucial for future biological research.

Purpose of the Study:

• To create an efficient and robust workflow for constructing cell-scale membrane envelopes.
• To embed membrane proteins into these envelopes for realistic simulations.
• To develop stable, large-scale membrane structures for molecular dynamics.

Main Methods:

• Implemented a subtractive assembly technique for membrane construction.
• Developed a structure concatenation tool (fastmerge) to eliminate overlapping elements volumetrically.
• Used MARTINI coarse-grained beads to represent cellular membranes in protocell models.

Main Results:

• Successfully constructed two protocell models (organelle and small bacterial cell sizes).
• Membrane envelopes remained stable during molecular dynamics simulations.
• Observed water flux only through specific proteins, indicating tight membrane compartments.
• Extended simulations revealed nonspecific protein interactions leading to microcluster formation.

Conclusions:

• The developed workflow enables the creation of stable, cell-scale membrane envelopes.
• This methodology is successful in building tight, cell-like membrane compartments for simulation.
• The findings provide a foundation for future cell-scale models incorporating more biological components.