MemBlob database and server for identifying transmembrane regions using cryo-EM maps.

Area of Science:

• Structural Biology
• Biophysics
• Computational Biology

Background:

• Identifying transmembrane helices in proteins is vital for understanding their function and developing therapeutics.
• Experimental data on membrane-embedded regions is limited, despite its presence in cryo-electron microscopy (cryo-EM) density maps.

Purpose of the Study:

• To develop a computational pipeline for determining membrane-embedded regions of proteins using cryo-EM data.
• To leverage underutilized information within cryo-EM maps for precise localization of transmembrane protein segments.

Main Methods:

• A computational pipeline was developed integrating cryo-EM maps and atomistic structures.
• The TMDET algorithm was used to determine potential bilayer orientation.
• Residues were classified into bulk water, lipid interface, and hydrophobic core categories.

Main Results:

• The pipeline successfully defines residues within different membrane environments (water, interface, hydrophobic core).
• A database of published cryo-EM structures with membrane region annotations was created.
• A server was developed for analyzing newly obtained cryo-EM structures.

Conclusions:

• The developed method effectively utilizes cryo-EM density maps to identify transmembrane protein regions.
• This approach provides valuable insights into protein-membrane interactions and can accelerate drug discovery.
• The created database and server offer accessible resources for researchers studying transmembrane proteins.