Structure analysis
Protein structure search
Search large protein-structure databases with a query fold, then inspect ranked neighbors, coverage, scores, and alignments.
Inputs
1 required
Methods
1 connected
- 01FoldSeek · Structure Database Search
FoldSeek performs the core structure search directly; downstream homology and function claims still require independent review.
Use this templateWhat is protein structure search?
Protein structure search is the process of querying a structural database with a three-dimensional protein model to find geometrically similar entries. FoldSeek represents local tertiary interactions with a structural alphabet, enabling fast candidate retrieval before detailed score, alignment, and biological review.
Use structure search to find remote homolog candidates, fold analogs, related domains, or structurally similar proteins when sequence search is insufficient. The query may be experimental or predicted, but chain choice, domain boundaries, missing residues, and model confidence affect retrieval.
ProteinIQ directly runs FoldSeek database search against supported structural collections. Results retain database identifiers, alignment statistics, TM-score and LDDT context, coverage, E-values, and files so promising hits can be checked with detailed pairwise alignment and independent biological evidence.
When to use protein structure search
- Best fit. Finding structural neighbors, remote homolog candidates, analogs, and fold-family context
- Required evidence. One reviewed protein structure with appropriate chain and domain boundaries
- Execution boundary. FoldSeek performs the core structure search directly; downstream homology and function claims still require independent review.
Benefits of protein structure search
- Structural sensitivity. Finds remote relationships missed by sequence search
- Connected evidence. Scales to large structural databases
- Reusable output. Returns inspectable alignments and method-native scores
Primary limitations
- Coverage limit. Database coverage limits what can be found
- Method dependence. Query boundaries and quality affect ranking
- Interpretive limit. Structural similarity alone does not prove function
Protein structure search methods
FoldSeek converts tertiary residue neighborhoods into a structural alphabet and applies sequence-search techniques to retrieve similar structures rapidly. Global shape-search and pairwise alignment methods use different representations and scoring objectives.
Database composition matters. Searching clustered predicted structures can reveal broad fold neighborhoods, while curated experimental structures may offer stronger ligand, assembly, and functional context.
Protein structure search applications
Protein structure search supports remote-homology discovery, structural annotation, fold classification, model-quality investigation, target comparison, and selection of templates or representatives for deeper analysis.
A match can reflect global fold, one shared domain, repetitive architecture, or local geometry. Inspect the aligned region rather than transferring annotations from the database record as a whole.
How to run protein structure search online
FoldSeek performs the core structure search directly; downstream homology and function claims still require independent review.
- Prepare the query. Choose the relevant chain, domain, assembly, and conformational state, and review missing or low-confidence regions.
- Choose databases. Select structural databases and thresholds that match the intended sensitivity and result volume.
- Run FoldSeek. Run FoldSeek while preserving database versions, search settings, warnings, and failed inputs.
- Review matches. Inspect rank, E-value, coverage, TM-score, LDDT, residue alignment, and query–target length differences together.
- Validate candidates. Confirm important candidates with detailed superposition, sequence evidence, curated annotations, and experiments when the claim requires them.
How to interpret protein structure search results
Evaluate E-value, score, coverage, aligned length, TM-score, LDDT, and sequence identity together. No single threshold is universal across query lengths, databases, and scientific questions.
Structural similarity is not proof of common ancestry or shared biochemical function. Confirm domain architecture, conserved residues, oligomeric state, ligands, taxonomy, and sequence evidence before annotation transfer.
How protein structure search works
FoldSeek performs the core structure search directly; downstream homology and function claims still require independent review.
- Prepare the query. Choose the relevant chain, domain, assembly, and conformational state, and review missing or low-confidence regions.
- Choose databases. Select structural databases and thresholds that match the intended sensitivity and result volume.
- Run FoldSeek. Run FoldSeek while preserving database versions, search settings, warnings, and failed inputs.
- Review matches. Inspect rank, E-value, coverage, TM-score, LDDT, residue alignment, and query–target length differences together.
- Validate candidates. Confirm important candidates with detailed superposition, sequence evidence, curated annotations, and experiments when the claim requires them.
Inputs and outputs
Check formats before running, then inspect and download the result from every workflow step.
Inputs
- Structure-analysis inputs.
PDBmmCIFFASTATSVOne experimental or predicted protein structure in PDB or mmCIF format.
Outputs
- Reviewable results.
PDBCSVTSVJSONFILESRanked database hits, identifiers, E-values, coverage, TM-scores, LDDT values, alignments, and downloadable files.
Tools for protein structure search
Use these methods to prepare inputs, run the core analysis, inspect outputs, and validate the evidence described in this workflow.
FoldSeek
Search structure databases or compare and cluster uploaded protein structures
USAlign
Align two protein structures and return TM-scores, RMSD, residue correspondence, and superposed coordinates
PDBFixer
Repair common coordinate-file issues before structural comparison
PDB Download
Retrieve experimental structures from the Protein Data Bank
AlphaFold Database Download
Retrieve predicted protein structures from the AlphaFold Protein Structure Database
PDB to FASTA converter
Extract protein sequences from coordinate files for sequence-aware review
HMMER
Search profile hidden Markov models for independent sequence-level homology evidence
MMseqs2
Search and cluster large protein sequence collections
DSSP
Assign secondary structure and solvent accessibility from protein coordinates
MolProbity
Check model geometry and steric quality before interpreting structural matches
SASA calculator
Calculate solvent-accessible surface area for matched structures
RMSD calculator
Superpose comparison structures on one reference and report RMSD values
Other structure analysis workflows
Compare related approaches based on the molecular system, available evidence, required inputs, and decision you need to support.
Protein fold recognition
Matches a protein sequence to known structural templates when ordinary sequence similarity is too weak to identify the fold reliably.
Multiple protein structure alignment
Places three or more protein structures into a shared correspondence for conserved-core, family, and evolutionary analysis.
Frequently asked questions
One experimental or predicted protein structure in PDB or mmCIF format.
Ranked database hits, identifiers, E-values, coverage, TM-scores, LDDT values, alignments, and downloadable files.
Confirm accession, model, chain, biological assembly, domain boundaries, residue numbering, missing regions, alternate conformations, and prediction confidence. Repair coordinates only when necessary and retain both the original file and every preparation decision.
Use method-native scores together rather than selecting one universal number. TM-score emphasizes length-normalized global fold similarity, RMSD reports geometric deviation over the aligned atoms, and coverage shows how much of each structure actually corresponds.
No. Similar folds can support different functions, and local similarity can occur without shared global architecture. Review residue-level correspondence, domains, ligands, oligomeric state, taxonomy, sequence evidence, curated annotations, and experiments.
A complete protein structure search project is generally quote-based. Current providers describe fold recognition and protein-structure analysis as customized services covering data review, method selection, modeling or comparison, validation, and interpretation rather than publishing one universal project price.
The cost depends on structure or sequence count, database scope, model preparation, method comparison, manual inspection, figures, annotation, and whether experimental follow-up is included. Open-source FoldSeek, US-align, and FoldMason can remove a software-license fee, but they do not remove expert analysis or compute requirements.
ProteinIQ self-service starts at $29 per month for academic Plus and $99 per month for commercial Pro, with the configured protein structure search workflow estimated in credits before submission. Done-for-you analysis is scoped separately.
Start with a workflow you can inspect and edit
Add your inputs, review the settings, and keep every structure, score, table, and file connected to the step that produced it.