# Homology modeling Build protein models from related experimental templates, then examine alignment assumptions, geometry, and structural agreement. [Open this workflow](https://proteiniq.io/app/workflows/templates?template=homology-model-review)[Contact sales](https://proteiniq.io/contact) ## More protein structure prediction workflows ## Tools for homology modeling Use these methods to prepare inputs, run the core analysis, inspect outputs, and validate the evidence described in this workflow. [![FoldSeek](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Ffoldseek.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### FoldSeek Search structural neighborhoods and related folds](https://proteiniq.io/app/foldseek)[![MMseqs2](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Fmmseqs2.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### MMseqs2 Search sequence homologs and candidate templates](https://proteiniq.io/app/mmseqs2)[![HMMER](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Fhmmer.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### HMMER Detect profile-supported protein family relationships](https://proteiniq.io/app/hmmer)[![PDBFixer](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Fpdb-fixer-featured.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### PDBFixer Repair common coordinate and atom issues](https://proteiniq.io/app/pdb-fixer)[![MolProbity](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Fmolprobity.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### MolProbity Assess clashes, rotamers, and stereochemistry](https://proteiniq.io/app/molprobity)[![Ramachandran plot](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Framachandran-plot.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### Ramachandran plot Inspect backbone torsion geometry](https://proteiniq.io/app/ramachandran-plot)[![USAlign](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Fusalign.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### USAlign Compare the model with a structural reference](https://proteiniq.io/app/usalign)[![DSSP](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Fdssp.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### DSSP Assign secondary structure from model coordinates](https://proteiniq.io/app/dssp)[![PROPKA 3](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Fpropka-3.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### PROPKA 3 Review structure-dependent ionization context](https://proteiniq.io/app/propka)[![PDBsum](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Fpdbsum.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### PDBsum Summarize structural contacts and architecture](https://proteiniq.io/app/pdbsum)[![SASA calculator](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Fsasa-calculator.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### SASA calculator Calculate residue and chain solvent exposure](https://proteiniq.io/app/sasa-calculator)[![Radius of gyration](https://proteiniq.io/_next/image?url=%2Fimages%2Ftools%2Fradius-of-gyration.webp&w=96&q=75&dpl=dpl_J8tu6aF3F41kEvMFgYtuMXes1ynJ) ### Radius of gyration Inspect global compactness](https://proteiniq.io/app/radius-of-gyration) ## What is homology modeling? Homology modeling, also called comparative modeling, is a method for building a target protein structure from one or more related proteins with experimentally determined structures. It aligns a target sequence to selected templates and transfers their structural framework, so reliability depends on template choice, alignment, insertions, loops, and side-chain treatment. A complete workflow searches and ranks templates, reviews a target–template alignment, constructs the model, and evaluates the result. Strong global sequence identity can still conceal errors around active sites, indels, domain boundaries, and long loops. ProteinIQ does not run a dedicated comparative-model builder. This workflow begins with a model generated by a specialist service or local package, then connects repair, stereochemical validation, and reference comparison without claiming that downstream tools generated the model. ### When to use homology modeling Use comparative modeling when a related experimental structure can support the region you care about: - A homolog has a trustworthy structure and meaningful target coverage. - The target–template alignment can be inspected around functional residues. - You need a structural starting model for experiments or further analysis. ### Strengths and limitations A suitable template gives the model a concrete structural basis, making conserved cores easier to interpret than an unconstrained fold prediction. Comparing the model with its template and other references can reveal where substitutions or domain boundaries may matter. The alignment can be wrong even when overall sequence identity is high. Insertions, flexible loops and alternative conformational states are difficult to transfer. ProteinIQ reviews an externally built comparative model; its geometry checks cannot recover an omitted or misaligned template segment. ## Homology-modeling decisions and interpretation Template selection should consider assembly, domain coverage, ligands, mutations, resolution, and conformational state, not sequence identity alone. Inspect the alignment manually near functional regions. Validation cannot prove a model correct, but it can identify implausible geometry and quantify similarity to a chosen reference. Retain the template identity, alignment, modeling settings, and every coordinate repair with the result. ## Applications of homology modeling A comparative model can supply a structural starting point when an experimentally determined homolog covers the region of interest. It is most useful for conserved domains with a clear target–template alignment; variable loops and insertions need more caution. The model can guide construct design or residue mapping, but a predicted active-site shape should be compared with template ligands and independent biochemical evidence before docking or mechanistic interpretation. ## How to run homology modeling online 1. **Choose a template externally.** Record the experimental structure, biological assembly, target coverage and sequence alignment used by a dedicated comparative-model builder. 2. **Build the model externally.** Retain the builder, settings, template identity and any loop-modeling choices with the resulting PDB. 3. **Repair the imported model.** Use [PDBFixer](https://proteiniq.io/app/pdb-fixer) for justified atom repairs and inspect every changed residue. 4. **Check stereochemistry.** Review [MolProbity](https://proteiniq.io/app/molprobity) outliers and backbone angles from [Ramachandran Plot](https://proteiniq.io/app/ramachandran-plot). 5. **Compare with a reference.** Use [US-align](https://proteiniq.io/app/usalign) against a relevant structure, then inspect local differences near the research question. ## How to interpret homology modeling results Geometry checks find strained atoms and unusual backbone angles, but cannot establish that a target–template alignment is correct. US-align reports structural similarity to the selected reference, not model accuracy where that reference differs biologically. Keep the template, alignment, model-building settings and repaired PDB together. A homology model can support prioritization and experiment planning; it does not confirm binding, activity or function. ## How homology modeling works Import an external comparative model, repair common coordinate issues, inspect geometry, and compare it with a selected reference structure. 1. **Select templates.** Search for structurally characterized homologs and select templates outside ProteinIQ. 2. **Review the alignment.** Review the target–template alignment, especially gaps, domain junctions, and functional residues. 3. **Build the model externally.** Generate the comparative model with a dedicated homology-modeling service or package. 4. **Check geometry and clashes.** Import the PDB into the ProteinIQ workflow and run PDBFixer, [MolProbity](https://proteiniq.io/app/molprobity), and Ramachandran Plot. 5. **Compare with structural evidence.** Use US-align against a relevant reference and export the model with its provenance and validation results. ## Inputs and outputs Check formats before running, then inspect and download the result from every workflow step. ### Inputs #### Research input `FASTA``PDB``mmCIF` An externally generated homology model in PDB format and, when available, a relevant experimental reference structure. ### Outputs #### Prediction and review outputs `PDB``mmCIF``CSV``JSON` A repaired model, MolProbity and Ramachandran geometry results, plus US-align structural comparison metrics. ## Frequently asked questions AI answers from our docs. 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