homology modeling
Definition
Homology modeling, also known as comparative modeling, is a computational technique for predicting the three-dimensional structure of a protein based on its amino acid sequence and the known structure of homologous proteins (templates). The method relies on the principle that evolutionarily related proteins with similar sequences adopt similar structural folds. Researchers identify template structures through sequence alignment, build a structural model by transferring spatial coordinates, and refine the model to optimize geometry and energy. Homology modeling is crucial when experimental structure determination via X-ray crystallography or cryo-EM is impractical, enabling structure-based drug design, functional annotation, and understanding protein-protein interactions for targets where only sequence information is available.
Visualize homology modeling in Nodes Bio
Researchers can visualize networks connecting query proteins to their homologous templates, displaying sequence identity percentages and structural coverage as edge weights. Nodes Bio enables mapping of modeled protein structures onto protein-protein interaction networks, identifying binding interfaces and druggable pockets within pathway contexts. Users can integrate homology model quality scores with functional annotations to prioritize targets for experimental validation or computational docking studies.
Visualization Ideas:
- Template-query protein similarity networks showing sequence identity and structural coverage relationships
- Protein domain architecture networks linking modeled structures to functional domains and binding sites
- Multi-species homology networks displaying evolutionary conservation of structural features across orthologs
Example Use Case
A pharmaceutical team investigating a novel kinase target in cancer lacks experimental structural data. They perform homology modeling using closely related kinase structures as templates, achieving 85% sequence identity. The resulting model reveals a unique ATP-binding pocket configuration. By visualizing the target kinase within its signaling pathway network in Nodes Bio, researchers identify potential allosteric sites and predict which downstream effectors might be affected by selective inhibitors, guiding medicinal chemistry efforts toward compounds with minimal off-target effects.