HOMCOS: an updated server to search and model complex 3D structures

Area of Science:

• Structural Biology
• Bioinformatics
• Computational Chemistry

Background:

• The Protein Data Bank (PDB) contains a vast collection of 3D molecular structures.
• Understanding the interactions between different molecules (proteins, nucleic acids, compounds, ions) is crucial for biological research.
• Existing tools may have limitations in comprehensively analyzing diverse molecular complexes.

Purpose of the Study:

• To update and enhance the HOMCOS server for comprehensive analysis of 3D molecular complexes within the PDB.
• To provide robust services for modeling protein multimers and protein-compound interactions.
• To enable prediction of interacting molecules for query proteins and compounds.

Main Methods:

• The HOMCOS server integrates BLAST and KCOMBU for similarity searches.
• Sequence-replaced modeling is employed for generating structural models of complexes.
• Flexible superposition using fkcombu is used for compound docking.
• Template-based docking is performed for monomeric query structures.
• Homology searching identifies potential interacting partners for query molecules.

Main Results:

• The updated HOMCOS server now includes all PDB molecules: proteins, nucleic acids, small compounds, and metal ions.
• Five distinct services are available: Homo Protein Multimer Modeling, Hetero Protein Multimer Modeling, Protein-Compound Complex Modeling, Searching Contact Molecules for a Query Protein, and Searching Contact Molecules for a Query Compound.
• Results are presented in user-friendly formats like "Summary Bars" and "Site Tables", with the latter facilitating mutation effect annotation.

Conclusions:

• The enhanced HOMCOS server offers a powerful and integrated platform for exploring and modeling diverse molecular interactions.
• It facilitates the prediction of binding partners and the analysis of complex structural relationships.
• The server's capabilities support various research applications, from structural biology to drug discovery and mutation analysis.