|What is I-TASSER server?|
|How does I-TASSER generate structure and function predictions?|
In the second step, the continuous fragments excised from the PDB templates are reassembled into full-length models by replica-exchange Monte Carlo simulations with the threading unaligned regions (mainly loops) built by ab initio modeling. In cases where no appropriate template is identified by LOMETS, I-TASSER will build the whole structures by ab initio modeling. The low free-energy states are identified by SPICKER through clustering the simulation decoys.
In the third step, the fragment assembly simulation is performed again starting from the SPICKER cluster centroids, where the spatial restrains collected from both the LOMETS templates and the PDB structures by TM-align are used to guide the simulations. The purpose of the second iteration is to remove the steric clash as well as to refine the global topology of the cluster centroids. The decoys generated in the second simulations are then clustered and the lowest energy structures are selected. The final full-atomic models are obtained by REMO which builds the atomic details from the selected I-TASSER decoys through the optimization of the hydrogen-bonding network (see Figure 1).
For predicting the biological function of the protein (the last column at Figure 1), the I-TASSER server matches the predicted 3D models to the proteins in 3 independent libraries which consist of proteins of known enzyme classification (EC) number, gene ontology (GO) vocabulary, and ligand-binding sites. The final results of function predictions are deduced from the consensus of top structural matches with the function scores calculated based on the confidence score of the I-TASSER structural models, the structural similarity between model and templates as evaluated by TM-score, and the sequence identity in the structurally aligned regions [A similar approach to structure-based function annotation was proposed by Brylinski and Skolnick (PNAS 2008. 205:129) who tried to match the target structures on the threading templates. Here the I-TASSER server matches the target models on all template proteins in the libraries].
|What are the performances of I-TASSER server compared with other methods?|
The I-TASSER server (as "Zhang-Server") participated in the Server Section of 7th (2006), 8th (2008), 9th (2010), and 10th CASPs (2012), and was ranked as the No 1 server in CASP7 and CASP8. In CASP9 and CASP10, I-TASSER server and QUARK (another server from our lab) were ranked as No 1 and No 2 servers, respectively. The detailed rank results can be seen here for CASP7, CASP8, CASP9, and CASP10. Figure 2 shows histograms of the Z-score of GDT-TS scores of all servers in CASP7 (68 servers), CASP8 (72 servers), CASP9 (81 servers), and CASP9 (72 servers).
Figure 3 is a summary of COFACTOR, a component of I-TASSER server, in the function prediction section of CASP9, where COFACTOR was registered as "I-TASSER_FUNCTION" and "Zhang" in the server and human prediction sections, respectively. The picture was taken from the presentation by the CASP9 assessor Dr. T Schwede, see http://predictioncenter.org/casp9/doc/presentations/CASP9_FN.pdf.
|What are the output of the I-TASSER server if you submit a seqeunce?|
|How to use known information (e.g. templates and function) to improve I-TASSER modeling?|
If users know some information about the structure of the modeled proteins, the information can be conveniently uploaded to the I-TASSER server. These information can significantly improve the quality of structural and function predictions.
The I-TASSER server currently accepts two types of user-specified restraints:
|Can I exclude some proteins from the I-TASSER template library?|
I-TASSER needs templates to generate high-resolution structure predictions. In general, excluding close templates will decrease the quality of the I-TASSER modeling. However, users can exclude some templates from the I-TASSER template library for some special purposes (e.g. knowning some templates are different from target, or benchmark testing of the current algorithms).
The I-TASSER server accept two ways of template excludings:
The format of the file should be "PDBID:ChainID %Sequence_Identity", e.g.
|What is new?|
|How long does it take for I-TASSER to generate the predictions for your protein?|
Currently, the major time consuming part in the I-TASSER protocol is the structural refinement assembly simulations. For those users who want a quicker reponse or those who do not need a refined models, we recommend them to use our LOMETS (meta-server) or MUSTER (single-server fold-recognition). Because these two servers do not attempt to refine the threading models, the response time is faster than the I-TASSER server.
|How to cite I-TASSER|
yangzhanglabumich.edu | (734) 647-1549 | 100 Washtenaw Avenue Ann Arbor, MI 48109-2218