Bigger isn't always better: Comparing system size, hydration, and software for lipid membrane analysis

Area of Science:

• Biophysics
• Computational Chemistry
• Materials Science

Background:

• Lipid membrane properties are crucial for cellular function.
• Molecular Dynamics (MD) simulations are vital for studying membrane dynamics.
• Analysis workflows and software choice can impact MD simulation results.

Purpose of the Study:

• To assess the convergence of structural and dynamic properties of POPC bilayers concerning membrane size and hydration.
• To compare the performance of four popular analysis software packages: CPPTRAJ (CPP), GROMACS (GRO), MDAnalysis (MDA), and LiPyphilic (LiP).

Main Methods:

• All-atom MD simulations were performed on 128, 256, 512, and 1024 POPC lipids.
• Simulations were conducted at hydration levels of 40, 80, and 160 water molecules per lipid.
• Structural properties (APL, thickness, order parameter, headgroup orientation) and lateral diffusion were analyzed using four software packages.

Main Results:

• Area per lipid, bilayer thickness, order parameter, and headgroup orientation were largely independent of system size and hydration.
• Lateral diffusion coefficient was sensitive to both size and hydration, with 128-lipid systems exhibiting artifacts at high hydration.
• Increasing system size reduced statistical variance for APL and thickness; all software packages yielded consistent APL and thickness results.

Conclusions:

• Moderately sized POPC systems (e.g., 256 lipids) are sufficient for reliable structural property analysis.
• CPPTRAJ offers an efficient serial analysis workflow for membrane properties.
• The choice of software and system size is critical for accurate MD-based membrane research.