Unattained geometric configurations of secondary structure elements in protein structural space

Area of Science:

• Structural Bioinformatics
• Computational Biology
• Protein Science

Background:

• Discovery of novel protein folds in the Protein Data Bank (PDB) has plateaued, leading to debate on whether all existing folds are documented or if sampling bias is a factor.
• An alternative perspective suggests that while all existing folds might be known, not all theoretically possible folds may have been discovered or documented.

Purpose of the Study:

• To investigate the completeness of the PDB by analyzing the geometric relationships between successive secondary structure elements (SSEs).
• To determine if all possible substructures formed by triplets of SSEs are represented in the PDB.
• To identify underrepresented motifs in one-dimensional sequences of SSE types.

Main Methods:

• Protein structures were simplified by representing them as sequences of alpha helices and beta sheets.
• Geometric relationships (torsion angles, lengths, distances) between successive SSEs were analyzed.
• SSEs were defined using both Promotif and DSSP assignment programs.
• One-dimensional sequences of SSE types were analyzed for underrepresented motifs.

Main Results:

• A gap in the representation of torsion angles for helix-strand-strand substructures was identified when using the Promotif program.
• This gap was not observed when using the DSSP program with a smaller minimum SSE length.
• Analysis of one-dimensional SSE sequences revealed that completely absent motifs occurred more frequently than expected by random chance.

Conclusions:

• The PDB may be incomplete, with potential gaps in represented SSE substructures and motifs.
• The existence of such gaps implies unexplored areas in protein structure space.
• The choice of SSE definition program can influence the identification of these gaps.