Using the CATH domain database to assign structures and functions to the genome sequences.

Area of Science:

• Structural bioinformatics
• Genomic annotation
• Computational biology

Background:

• The CATH database classifies protein structures, aiding evolutionary and functional analysis.
• Sequence search methods are crucial for identifying homologous proteins across databases.
• Understanding protein function is vital for deciphering biological mechanisms.

Purpose of the Study:

• To evaluate the effectiveness of sequence search methods for annotating microbial genomes using the CATH database.
• To assess the reliability of inferring protein function based on structural and evolutionary relationships.

Main Methods:

• Utilized the CATH database of protein structures.
• Tested various sequence search methods, including gapped BLAST and Position Specific Iterated Basic Local Alignment Tool (PSI-BLAST).
• Analyzed functional conservation within CATH's fold groups and homologous superfamilies.

Main Results:

• PSI-BLAST and gapped BLAST can assign structural data to 22-36% of microbial genomes.
• Functional conservation is high in enzyme families (nearly 55%), but divergence occurs in some large families.
• Caution is advised when inferring function in highly populated families due to potential divergence.

Conclusions:

• Sensitive sequence search algorithms can enhance microbial genome annotation.
• Functional inference based on homology requires careful consideration of potential divergence, especially in large protein families.
• Further assessment of key residue substitutions is recommended for accurate functional prediction.