MEPSi: A tool for simulating tomograms of membrane-embedded proteins.

Area of Science:

• Structural Biology
• Biophysics
• Microscopy

Background:

• Cryo-electron tomography (cryo-ET) is advancing rapidly, but remains costly and time-consuming due to complex sample preparation and equipment requirements.
• Assessing the suitability of imaging parameters for specific biological questions is typically only possible after data acquisition and reconstruction, leading to potential wasted effort.

Purpose of the Study:

• To introduce MEPSi (Membrane Embedded Protein Simulator), a novel simulation tool designed for efficient evaluation and optimization of cryo-ET data acquisition parameters.
• To facilitate the study of transmembrane proteins within their native membrane environments.

Main Methods:

• MEPSi was developed to simulate cryo-ET data acquisition, allowing for the assessment of various imaging parameters.
• The tool was tested using simulated plasma membranes with embedded αIIbβ3 integrin receptors and simulated virus membranes with SARS-CoV-2 spike proteins.

Main Results:

• MEPSi enables the rapid and convenient evaluation of cryo-ET data acquisition parameters.
• The simulation tool allows for the disentanglement of the influence of different data collection parameters and sample orientations relative to the tilt axis and electron beam.

Conclusions:

• MEPSi provides a valuable resource for optimizing cryo-ET experiments before data acquisition, potentially reducing costs and improving the efficiency of structural studies.
• This simulation tool can aid researchers in determining the feasibility of cryo-ET for specific biological questions and optimizing imaging strategies for transmembrane proteins.