From molecular dynamics to cryo-EM: Imaging liposomes in silico
Karan Sharma1, Frederick A Heberle2, Milka Doktorova1
1Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, Solna, Sweden.
Methods in Enzymology
|March 1, 2026
Summary
This study links molecular dynamics (MD) simulations with cryogenic electron microscopy (cryo-EM) to create synthetic images of lipid bilayers. This computational framework validates analysis tools and refines understanding of membrane organization.
Area of Science:
- Biophysics
- Structural Biology
- Computational Biology
Background:
- Cryogenic electron microscopy (cryo-EM) offers nanometer resolution for lipid bilayer structure.
- Molecular dynamics (MD) simulations accurately model lipid packing and membrane properties.
Purpose of the Study:
- To present a computational framework linking MD simulations and cryo-EM.
- To generate synthetic cryo-EM projection images from MD simulations of lipid bilayers.
Main Methods:
- Forward modeling approach using MD simulations of flat bilayer patches.
- Calculating electron scattering and phase-shift profiles from simulated densities.
- Mapping profiles onto vesicles, projecting, and convolving with contrast transfer function.
Main Results:
- Generation of realistic synthetic cryo-EM images from MD simulations.
- Strategies for noise incorporation and analysis of radial intensity profiles.
- Benchmarks against experimental cryo-EM data validating the workflow.
Conclusions:
- The MD-to-cryo-EM workflow enables ground-truth comparisons between simulated and experimental data.
- Facilitates validation of analysis tools and resolution limit probing for bilayer features.
- Enhances understanding of membrane organization at the single-vesicle level.
Keywords:
atomic number density profilebilayer structurecryogenic electron microscopylipid vesiclemembrane dipole potentialmolecular dynamics simulationsphase separation
