Detect distant homology to proteins of known structure

Compare a sequence against a set of profiles or perform profile-profile comparison.

Layer on structural information

ebisu group

chemogenomix © 2012

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Fold Recognition (GenTHREADER)

GenTHREADER is a fast and relatively powerful fold recognition method, which can be applied to either whole, translated genomic sequences (proteomes) as in the case of the GTD or individual protein sequences as in the case of the PSIPRED server. It is not as sensitive at mGenTHREADER but is much faster.

Fold Recognition (pGenTHREADER)

This method is now our recommended method for fold recognition and identification of distant homologues. Essentially it is the based on the original GenTHREADER method, but makes use of profile-profile alignments and predicted secondary structure (using PSIPRED) as inputs. This increases both the sensitivity of the method and enhances the accuracy of alignments, but also makes it much slower than the normal GenTHREADER method as PSI-BLAST needs to be run on the target sequence before the search can begin.

Domain Recognition (pDomTHREADER)

pDomTHREADER is an accurate and sensitive superfamily discrimination, combining information from both sequence and structure to produce highly accurate domain alignments. The method employs the same underlying threading algorithm as pGenTHREADER, however it aligns sequences to a domain-based template library rather than a chain-based template library. The use of smaller regions of structure for templates means that different features of the alignments are required for optimal scoring. The final prediction score results from an SVM trained on a combination of 5 different feature inputs; template coverage, alignment score, template length, solvation and pairwise potentials.

Compared with other superfamily discrimination methods using Hidden Markov Models and PSI-BLAST profile alignments, pDomTHREADER provided higher coverage on the CATH S35 superfamilies. Additionally, pDomTHREADER produced more accurate alignments that can be used to better predict domain boundaries. For more information regarding the method, please consult the reference above.

Please note that the pDomTHREADER method is tuned for performance in fine superfamily discrimination, for fold recognition problems or structural annotation of very distant sequences, pGenTHREADER should be used.

The information described here is taken from the Bioinformatics group web site run by Prof David Jones at University College London


GenThreader is a family of programs designed to detect distant evolutionary relationships. The original GenThreader algorithm was published in 1999 and subsequent versions have both refined the concept and adapted the implementation to make use of increased availability of protein sequence data.