An interpretable alphabet for local protein structure search based on amino acid neighborhoods.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40848287", "kind": "science-record", "revision": 2, "content_hash": "sha256:d1c6cff9c908af76eec1cdf3309523870ad78ffa24e47b683aed60424b7ead93", "created_at": "2026-11-01T20:30:57Z", "updated_at": "2026-11-01T21:35:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "An interpretable alphabet for local protein structure search based on amino acid neighborhoods.", "doi": "10.1093/bioinformatics/btaf458", "pmid": "40848287", "authors": ["Saba Zerefa", "Jesse Cool", "Pramesh Singh", "Samantha Petti"], "journal": "Bioinformatics (Oxford, England)", "year": 2025, "abstract": "MOTIVATION: Recent advancements in protein structure prediction methods have vastly increased the size of databases of protein structures, necessitating fast methods for protein structure comparison. Search methods that find structurally similar proteins can be applied to find remote homologs, study the functional relationships among proteins, and aid in protein engineering tasks.\nRESULTS: We design a \"3Dn\" structural alphabet that encodes the local neighborhoods around each amino acid in an interpretable way. In a search benchmark task, a combination of our alphabet and Foldseek's 3Di alphabet, outperforms each alphabet individually and ranks best among local search methods that do not require amino acid identity information. We provide software tools that enable the exploration of novel alphabets and combinations of alphabets for protein structure search.\nAVAILABILITY AND IMPLEMENTATION: The code is freely available at https://github.com/spetti/structure_comparison and at Zenodo https://doi.org/10.5281/zenodo.15734371.", "claims": [{"id": "claim-method", "statement": "The efficacy of each query is evaluated using sensitivity up to the first false positive across family, superfamily, and fold levels, which is the ratio of the number of true positives before the first false positive to the total number of true positives at each classification level.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40848287", "locator": "sections[13] \"3.1 Search benchmark\" paragraph 2", "quote": "The efficacy of each query is evaluated using sensitivity up to the first false positive across family, superfamily, and fold levels, which is the ratio of the number of true positives before the first false positive to the total number of true positives at each classification level."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data underyling this article are available in https://github.com/spetti/structure_comparison and at Zenodo https://doi.org/10.5281/zenodo.15734371. The datasets were derived from sources in the public domain, particularly SCOPe https://scop.berkeley.edu/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40848287", "locator": "sections[26] \"Data availability\" paragraph 2", "quote": "The data underyling this article are available in https://github.com/spetti/structure_comparison and at Zenodo https://doi.org/10.5281/zenodo.15734371. The datasets were derived from sources in the public domain, particularly SCOPe https://scop.berkeley.edu/."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40848287"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40848287", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1093/bioinformatics/btaf458", "sha256": "sha256:c75c78399b5932053d92b11bd55b3d250f37a6307f5eca4679e8a63bab103506", "bytes": 49934, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1093/bioinformatics/btaf458", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12516309", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "sensitivity up to the first false positive", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The efficacy of each query is evaluated using sensitivity up to the first false positive across family, superfamily, and fold levels, which is the ratio of the number of true positives before the first false positive to the total number of true positives at each classification level."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (sensitivity up to the first false positive), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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