Enabling Atomistic Modeling and Simulation of Complex Curved Cellular Membranes with xMAS Builder

Area of Science:

• Computational Biology
• Biophysics
• Cell Biology

Background:

• Cellular membranes perform vital functions but are challenging to model at the atomistic level due to their size and complexity.
• Advancements in high-performance computing enable cell-scale molecular dynamics (MD) simulations.
• Existing methods struggle to build accurate, large-scale membrane models from experimental data.

Purpose of the Study:

• To introduce xMAS Builder, a novel tool for constructing atomistic models of complex cellular membranes.
• To utilize experimental lipidomics and structural data for building MD-ready membrane models.
• To investigate the biophysical properties of large-scale, experimentally-derived membrane models.

Main Methods:

• Developed xMAS Builder (Experimentally-Derived Membranes of Arbitrary Shape Builder) software.
• Input experimental lipidomics and structural data (electron microscopy, tomography).
• Generated two large-scale (11-12 million atoms) membrane models with varying lipid packing densities.
• Performed extended molecular dynamics (MD) simulations (250 ns and 386 ns) on the models.

Main Results:

• xMAS Builder successfully generated two large, complex membrane models.
• Both models maintained membrane integrity during long MD simulations.
• Divergent relaxation dynamics revealed leaflet volume, not surface area, determines packing density in curved membranes.

Conclusions:

• xMAS Builder algorithms produce high-quality, MD-ready models of cellular membranes.
• Simulation of these models offers profound biophysical insights into membrane behavior.
• Leaflet volume is a critical factor for understanding packing density in curved biological membranes.