Expectations from structural genomics revisited: an analysis of structural genomics targets

Area of Science:

• Structural biology
• Genomics
• Bioinformatics

Background:

• Structural genomics aims to catalog protein folds for comparative modeling and functional inference.
• Protein structure determination can reveal novel folds or similarities to known structures.
• Functional insights depend on homologous sequences and their characterization.

Purpose of the Study:

• To analyze structural genomics target sequences for functional family membership.
• To predict the potential functional insights obtainable from structural genomics projects.

Main Methods:

• Sequence searching methods were employed to analyze target sequences.
• Classification into functionally characterized, unknown function, or orphan protein families was performed.
• Analysis utilized the PFAM database (protein families database of alignments and hidden Markov models).

Main Results:

• Approximately 25% of unannotated protein families in PFAM were matched.
• 16% of sequences were strict orphans, posing challenges if novel folds emerge.
• 28% of targets matched families with unknown function but considerable sequence diversity.

Conclusions:

• New protein structures from diverse families offer functional insights, even with novel folds.
• Mapping sequence conservation onto structures can identify key residues for experimental study.