CS-BLAST is an extension to standard NCBI BLAST that allows to increase its sensitivity by a factor of more than two on remote homologs at the same speed. CS-BLAST first adds context-specific pseudocounts to the input sequence and then jumpstarts PSI-BLAST with the resulting profile. The output is identical to BLAST and contains a list of closest homologs with alignments.
The software can be downloaded here.



Remote homology detection method based on iterative HMM-HMM comparison. HHblits can build high-quality MSAs starting from single sequences or from MSAs. It transforms these into a query HMM and iteratively searches through uniprot20 or nr20 databases by adding significantly similar sequences from the previous search to the updated query HMM for the next search iteration. Compared to PSI-BLAST, HHblits is faster, up to twice as sensitive and produces more accurate alignments.
The HHblits software is part of the open source package HHsuite.



Sensitive protein homology detection and structure prediction by HMM-HMM-comparison. Starting from a query sequence, HHpred builds a multiple sequence alignment using HHblits and turns it into a profile HMM. This is then compared it with a database of HMMs representing proteins with known structure (e.g. PDB, SCOP) or annotated protein families (e.g. PFAM, SMART, CDD, COGs, KOGs). The output is a list of closest homologs with alignments. HHpred can also build 3d homology models using the identified templates in the PDB database. It can optimize template picking and query-template alignments for homology modeling.
The HHblits software is part of the open source package HHsuite.



Sensitive intermediate profile search using HMM-HMM comparison. HHsenser takes a sequence or an alignment as input and builds an alignment with as many near or remote homologs as possible. It uses representative sequences in the vicinity of the input alignment as seeds to build new alignments with PSI-BLAST. The process continues until all seeds have been processed. The runtime may be 30 min up to several hours depending on input parameters.



Fast, PSI-BLAST accelerated HMMER search. About 30 times faster for the nr database.



Retrieves all sequences which contain a given PROSITE pattern or regular expression.



Search with an amino acid sequence against protein databases for locally similar sequences.



Search with an amino acid sequence against protein databases for locally similar sequences. Similar to ProteinBLAST but more sensitive. PSI-BLAST first performs a BLAST search and builds an alignment from the best local hits. This alignment is then used as a query for the next round of search. After each successive round the search alignment is updated.



SimShiftDB builds alignments between a query protein with unknown structure (for which chemical shifts for HA,H,N,CA,CB, or CO are available) and a database of template proteins whose 3D structure is known. The alignments are scored by an E-Value indication (similar to the E-Value calculated by BLAST).



PDBalert is a web-based automatic system that alerts users as soon as a pdb structure with homology to a protein of interest becomes available. Users can upload their personal protein sequences of interest. Once a week, when new proteins are released to the PDB database, PDBalert compares these with the users' sequences. When a significant match is found, the user is alerted by an email containing a link to the search results.


Nucleotide Blast

Search with a nucleotide sequence against nucleotide databases for locally similar sequences with tblastn.



Search your protein with the InterPro database of protein families, domains and functional sites in which identifiable features found in known proteins can be applied to unknown protein sequences. InterPro contains many databases of HMMs or patterns, such as Pfam, PANTHER, SMART, TIGRFAMs, PIRSF, PRODOM, CATH, SUPERFAMILY, PRINTS, and PROSITE.



Search your protein sequence with the Pfam database of HMMs for known protein domains (including modular domains and repeat families). The Pfam database contains a large collection of curated and relatively well-annotated alignments/HMMs.



Search your protein sequence with the SMART database of HMMs for known modular domains and repeat families. The database alignments/HMMs are hand-curated and very well annotated.



Search your protein sequence with a database of HMMs for known repeat families, such as Ankyrin, Armadillo, HAT, HEAT, Kelch, LRR, PFTA, PFTB, RCC1, TPR, WD40.



Prediction of Eukaryotic Linear Motifs, a special class of functional sites in eukaryotic proteins. Putative functional sites are identified by patterns. To improve the predictive power, context-based rules and logical filters are applied.



Search your protein for motifs likely to be phosphorylated by a specific protein kinases or to bind to domains such as SH2 domains, 14-3-3 domains or PDZ domains. Uses sequence profiles instead of patterns.