MemBlob

MemBlob determines membrane boundaries of transmembrane proteins from cryo-electron microscopy (cryo-EM) density maps to assign residues to membrane phases and estimate protein–lipid interface residues.

Key Features:

• Utilization of cryo-EM density maps: Uses cryo-EM density maps to delineate regions of transmembrane proteins embedded in lipid bilayers by leveraging nonprotein density signals.
• Computational inputs: Integrates a cryo-EM density map and an atomistic protein structure with bilayer orientation information provided by the TMDET algorithm.
• Residue phase assignment: Assigns residues to membrane-related phases: bulk water phase, lipid interface, and lipid hydrophobic core.
• Estimation of membrane-contacting residues: Estimates surface residues interacting with the membrane using structural models and experimental electron density maps.

Scientific Applications:

• Mechanistic studies: Maps precise positioning of transmembrane proteins within lipid bilayers to inform mechanisms of action.
• Drug development: Provides detailed membrane-region mapping to support therapeutic targeting of channels, pores, and receptors.
• Proteome research: Enhances structural characterization and annotation of transmembrane components of the proteome relative to soluble, globular proteins.

Methodology:

Computationally integrates cryo-EM density maps, atomistic protein structures, and TMDET-derived bilayer orientations; extracts nonprotein density signals to delineate membrane regions, assigns residues to bulk water phase, lipid interface, or lipid hydrophobic core, and estimates membrane-contacting surface residues from structural models and experimental electron density maps.