available. Thus, batch jobs will often take longer than individually submitted jobs, but this is necessary to allow a fair distribution of computing resources to all Phyre2 users. One to one threading One to one threading allows you to upload both a sequence you wish modelled AND the template on which to model it. Users sometimes have a protein sequence that they wish to model on a specific template of their choice. This may be for example a newly solved structure that is not in the Phyre2 database or because of some additional biological information that indicates the chosen template would produce a more accurate model than the one(s) automatically chosen by Phyre2. Backphyre Instead of predicting the 3D structure of a protein sequence, often users have a solved structure and they are interested in determining if there is a related structure in a genome of interest. In Phyre2 an uploaded protein structure can be converted into a hidden Markov model and then scanned against a set of genomes (more than 20 genomes as of March 2011). This functionality is called "BackPhyre" to indicate how Phyre2 is being used in reverse. Phyrealarm Sometimes Phyre2 can't detect any confident matches to known structures. However, the fold library database increases by about 40-100 new structures each week. So even though there might be no decent templates this week, there may well be in the coming weeks. Phyrealarm allows users to submit a protein sequence to be automatically scanned against new entries added to the fold library every week. If a confident hit is detected, the user is automatically notified by email together with the results of the Phyre2 search. Users can also control the level of alignment coverage and confidence in the match required to trigger an email alert. 3DLigandSite Phyre2 is coupled to the 3DLigandSite server for protein binding site prediction. 3DLigandSite has been one of the top performing servers for binding site prediction at the Critical Assessment of Techniques for Protein Structure Prediction (CASP) in (CASP8 and CASP9). Confident models produced by Phyre2 (confidence >90%) are automatically submitted to 3DLigandSite. Transmembrane topology prediction The program memsat_svm is used to predict the presence and topology of any transmembrane helices present in the user protein sequence. Multi-template modelling Phyre2 permits users to choose 'Intensive' modelling from the main submission screen. This mode: Examines the list of hits and applies heuristics in order