Leri: A web-server for identifying protein functional networks from evolutionary couplings.

Area of Science:

• Biochemistry
• Computational Biology
• Structural Biology

Background:

• Co-evolutionary information of amino acid pairs is crucial for protein engineering, mutation design, and structure prediction.
• Identifying functional residues and their networks is essential for understanding protein mechanisms.

Purpose of the Study:

• To develop and present a method for identifying networks of residues, termed "residue communities", relevant to protein function using co-evolutionary data.
• To establish a webserver for analyzing protein families and discovering functional sites and biological pathways.

Main Methods:

• Estimated co-evolution information was used to identify significant protein determinants.
• Residue communities were identified and analyzed for their correlation with functional sites.
• A benchmark dataset of 67 proteins and the endoplasmic reticulum-mitochondria encounter structure complex were used for validation.

Main Results:

• The method identified residue communities relevant to protein function.
• A high Pearson's correlation (0.53, >0.8 with conserved residues) was observed between identified residues in communities at functional sites.
• Three distinguishable residue communities relevant to functional roles were identified in the endoplasmic reticulum-mitochondria complex, suggesting general evolutionary signatures.

Conclusions:

• Residue communities identified through co-evolutionary analysis represent significant evolutionary signatures in proteins.
• The developed method and webserver provide a powerful tool for analyzing protein families, discovering functional sites, and identifying biological pathways.