CC⁺ : A searchable database of validated coiled coils in PDB structures and AlphaFold2 models

Area of Science:

• Structural biology
• Bioinformatics
• Computational biology

Background:

• Alpha-helical coiled coils are fundamental protein structural motifs involved in various biological processes.
• Predicting coiled-coil structures from sequence alone can be challenging, with heptad repeat analysis having limitations.
• The SOCKET program and the CC+ database were previously developed to identify and analyze coiled-coil structures.

Purpose of the Study:

• To update the CC+ database with new protein structures and an improved SOCKET analysis tool (Socket2).
• To incorporate AlphaFold2-predicted structures into the CC+ database.
• To provide a comprehensive resource for exploring coiled-coil assemblies, their sequence-structure relationships, and facilitating protein design.

Main Methods:

• Utilized the updated SOCKET (Socket2) program to analyze protein structures from the Protein Data Bank (PDB).
• Integrated experimentally determined coiled-coil structures and AlphaFold2-predicted structures into the CC+ relational database.
• Applied stringent SOCKET parameters for high-confidence coiled-coil identification.

Main Results:

• The updated CC+ database contains approximately 12,000 experimentally determined coiled-coil assemblies.
• The database includes around 120,000 potential coiled-coil structures predicted by AlphaFold2 across 48 proteomes.
• CC+ allows searching and visualization of coiled coils at multiple levels (structure, sequence, interactions).

Conclusions:

• The enhanced CC+ database provides an expanded resource for studying coiled-coil protein structures.
• The integration of AlphaFold2 predictions significantly increases the scope of identifiable potential coiled coils.
• CC+ serves as a valuable tool for understanding protein structure-function relationships and advancing protein engineering efforts.