Biological Databases & Search Tools

A no-fluff reference directory — the open places to search proteins, promoters, structures, interactions, and the engines that query them.

What this is

The open places to search biology — sequences, structures, promoters, interactions, expression, variants, chemistry — plus the search engines, alignment tools, and REST APIs / libraries that query them. Every row links to its real home. Links verified resolving 2026-07-04.

Databases

Sequence & protein

Name	What it holds
UniProt	Curated (Swiss-Prot) + automatic (TrEMBL) protein sequences & functional annotation.
NCBI Protein	Aggregated protein sequences from GenBank, RefSeq, PDB, Swiss-Prot.
NCBI RefSeq	Non-redundant curated reference sequences — DNA, RNA, protein.
NCBI Entrez	Cross-database search portal over all NCBI resources.
Ensembl	Vertebrate genome annotation, gene models, comparative genomics.
EMBL-EBI	Umbrella portal — UniProt, InterPro, PDBe, Ensembl, ArrayExpress.
InterPro	Integrated protein families, domains, functional sites across member DBs.
Pfam	Protein family HMM profiles, now served within InterPro.
PROSITE	Protein domains, families, functional-site patterns & profiles.
PRINTS	Protein fingerprints (conserved motif groups); via InterPro.

Structure

Name	What it holds
RCSB PDB	US portal to the Protein Data Bank — experimental 3D macromolecular structures.
PDBe	European PDB node with analysis & validation tools.
PDBj	Japanese PDB archive node.
AlphaFold DB	AlphaFold2 predicted structures for >200M sequences (EBI).
ESM Metagenomic Atlas	ESMFold-predicted structures for hundreds of millions of metagenomic proteins.
EMDB	Electron Microscopy Data Bank — 3D cryo-EM/ET density maps.
BMRB	Biological Magnetic Resonance Data Bank — NMR spectral/structural data.

Promoters & gene regulation

Name	What it holds
EPD	Eukaryotic Promoter Database — experimentally validated POL II promoters/TSS.
JASPAR	Curated, non-redundant TF binding profiles (position frequency matrices).
HOCOMOCO	Human & mouse TF binding models from ChIP-seq.
RegulonDB	E. coli K-12 transcriptional regulation — operons, promoters, TF sites.
ENCODE	Functional genomic elements — ChIP-seq, DNase, RNA-seq across cell types.
Ensembl Regulatory Build	Genome-wide regulatory features — promoters, enhancers, CTCF, TFBS.
ORegAnno	Community-curated regulatory regions, TFBS, regulatory polymorphisms (via UCSC track).
FANTOM5 / CAGE	CAGE-defined promoters & enhancers, transcription start-site atlas.
footprintDB	DNA motifs and cognate TF binding interfaces across curated libraries.

Interactions & pathways

Name	What it holds
STRING	Known & predicted protein-protein functional associations.
BioGRID	Curated genetic & protein interactions, chemical & PTM data.
IntAct	Curated molecular interaction data — binary & complex.
Reactome	Curated human biological pathways & reactions.
KEGG	Pathway maps, genomes, compounds, diseases, drugs.
WikiPathways	Community-curated, open biological pathway models.
OmniPath	Integrated signaling, regulation & interaction resource.
SIGNOR	Curated causal signaling relationships between biological entities.

Expression / single-cell

Name	What it holds
GEO	Gene Expression Omnibus — functional genomics data repository.
ArrayExpress / BioStudies	Functional genomics experiments & structured study metadata (EBI).
GTEx	Tissue-specific gene expression & eQTLs across human donors.
Human Protein Atlas	Protein expression across tissues, cells, cancers via imaging.
Expression Atlas	Baseline & differential gene/protein expression across conditions.
CELLxGENE	Explore & download standardized single-cell datasets (CZI).
Single Cell Portal	Host, visualize & share single-cell RNA-seq studies (Broad).
Human Cell Atlas	Reference maps of all human cell types (data portal).

Variants / genomes

Name	What it holds
dbSNP	Short genetic variations — SNPs, indels, microsatellites.
ClinVar	Variant-phenotype relationships with clinical significance.
gnomAD	Population allele frequencies from aggregated exomes & genomes.
UCSC Genome Browser	Genome sequence with layered annotation tracks.
COSMIC	Catalogue of somatic mutations in cancer (Sanger).

Chem / drug

Name	What it holds
ChEMBL	Bioactive drug-like molecules with binding & ADMET data (EBI).
PubChem	Chemical structures, bioassays, and substance data (NCBI).
DrugBank	Drug targets, mechanisms, interactions & pharmacology.
BindingDB	Measured binding affinities of protein-ligand pairs.
ZINC	Purchasable compounds for virtual screening & docking.

Search tools & alignment engines

Sequence search / alignment

Name	What it does	Lang
NCBI BLAST	Reference similarity search; web + `blast+` CLI + URLAPI.	C++
EBI BLAST (JDispatcher)	EBI-hosted BLAST/FASTA/HMMER REST job dispatcher.	Perl/Java
DIAMOND	100–20000× faster protein/translated aligner vs BLASTX.	C++
MMseqs2	Ultra-fast, sensitive many-vs-many protein/nt search & clustering.	C++
HMMER	Profile-HMM search (hmmsearch/hmmscan/phmmer) against Pfam etc.	C
VSEARCH	Open USEARCH replacement: search/cluster/dereplicate/chimera.	C++
USEARCH	Fast search/clustering, now open-sourced.	C++
minimap2	Long-read / genome-to-genome & spliced aligner (mapping).	C
HH-suite	HMM-HMM remote-homology search (HHblits/HHsearch).	C++

Structure search

Name	What it does	Lang
Foldseek	Structure search at BLAST-like speed via 3Di alphabet; AFDB-scale.	C++
DALI	Distance-matrix structural alignment server.	Fortran/Perl
TM-align	TM-score-optimal pairwise structure superposition.	C++

Motif / promoter search

Name	What it does	Lang
MEME Suite	Motif discovery + scanning (MEME, STREME, Tomtom, FIMO).	C/Perl
FIMO	Scan sequences for occurrences of a known PWM motif.	C
JASPAR API	Open TF-binding PWM database + REST API.	web
HOMER	Motif discovery + NGS peak/enhancer analysis suite.	Perl/C
PWMScan (EPD)	Genome-wide PWM matching against EPD promoters.	C/web

Rust / systems angle

The fast search engines are all C/C++ — DIAMOND, MMseqs2, Foldseek, minimap2, HMMER, VSEARCH. That's the systems-rewrite gap. Rust covers the primitives but not the full pipeline: sourmash (MinHash/FracMinHash k-mer sketch search), needletail (FASTA/FASTQ + k-mer iteration), block-aligner (SIMD Smith-Waterman/Needleman-Wunsch), rust-bio (alignment, FM-index), noodles (pure-Rust BAM/CRAM/VCF I/O). No full-sensitivity Rust replacement for MMseqs2/DIAMOND/Foldseek exists yet — the sensitive prefilter-and-align pipeline is the open build target.

Programmatic libraries & REST APIs

Query libraries

Name	What it does	Lang
Biopython	Swiss-army toolkit; parsers, Entrez, BLAST, seq objects.	Python
Biotite	Fast NumPy-backed seq/structure lib + DB fetch (RCSB/NCBI/UniProt).	Python/C
gget	One-line queries to UniProt/Ensembl/NCBI/AlphaFold/PDB/BLAST.	Python
bioservices	Unified wrappers over 40+ bio web services / REST APIs.	Python
mygene	One-call gene annotation via MyGene.info.	Python
PyEnsembl	Local Ensembl genome/annotation query API.	Python
pysam	htslib bindings: BAM/CRAM/VCF/tabix access.	Python/C
rentrez	R client for NCBI Entrez / E-utilities.	R
biomaRt	Bioconductor client to Ensembl BioMart.	R
InterMine	Federated genomic data-warehouse + Py/R/JS API clients.	Java
kb_python	kallisto\|bustools scRNA workflow wrapper.	Python

REST APIs

Name	What it does	Type
UniProt REST	Protein records, ID mapping, streaming queries.	REST
Ensembl REST	Genes/transcripts/variants/xrefs/homology across species.	REST
NCBI E-utilities	esearch/efetch/elink across all NCBI databases.	REST
RCSB Data API	Structured PDB entry/assembly/annotation (REST + GraphQL).	REST
EBI Search	Cross-domain search over EBI's data resources.	REST