FOLD-EM

FOLD-EM identifies and models folded macromolecular domains within medium to low resolution (4–15 Å) cryo-electron microscopy (cryo-EM) density maps to support interpretation of large multi-component biological assemblies.

Key Features:

• Automated Domain Identification: FOLD-EM automatically detects independently folded domains within complex macromolecular assemblies from cryo-EM density maps.
• Hybrid Structural Approach: Fits high-resolution atomic models or suitable homologs into lower-resolution cryo-EM maps to improve structural interpretation.
• Structural Homology Search: Systematically searches for structural homologs even when sequence homology is undetectable.
• Mosaic Backbone Model Construction: Constructs a mosaic backbone model by fitting representative domain structures from a protein domain database into the cryo-EM map.
• Flexible Multi-Domain Fitting: Performs flexible multi-domain fitting to explore conformational variability within assemblies.

Scientific Applications:

• Structural biology of large assemblies: Enables interpretation of the architecture and function of large multi-component biological assemblies from medium to low resolution cryo-EM maps.
• Polypeptide modeling and mechanism inference: Provides detailed models of constituent polypeptides to support elucidation of molecular mechanisms and interactions.

Methodology:

FOLD-EM utilizes the computational principles of the Scale-Invariant Feature Transform (SIFT) for identification and fitting of domain structures, accommodating variations in scale and orientation in cryo-EM data.