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. 2010 Apr;5(4):725-38.
doi: 10.1038/nprot.2010.5. Epub 2010 Mar 25.

I-TASSER: A Unified Platform for Automated Protein Structure and Function Prediction

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Free PMC article

I-TASSER: A Unified Platform for Automated Protein Structure and Function Prediction

Ambrish Roy et al. Nat Protoc. .
Free PMC article

Abstract

The iterative threading assembly refinement (I-TASSER) server is an integrated platform for automated protein structure and function prediction based on the sequence-to-structure-to-function paradigm. Starting from an amino acid sequence, I-TASSER first generates three-dimensional (3D) atomic models from multiple threading alignments and iterative structural assembly simulations. The function of the protein is then inferred by structurally matching the 3D models with other known proteins. The output from a typical server run contains full-length secondary and tertiary structure predictions, and functional annotations on ligand-binding sites, Enzyme Commission numbers and Gene Ontology terms. An estimate of accuracy of the predictions is provided based on the confidence score of the modeling. This protocol provides new insights and guidelines for designing of online server systems for the state-of-the-art protein structure and function predictions. The server is available at http://zhanglab.ccmb.med.umich.edu/I-TASSER.

Conflict of interest statement

COMPETING FINANCIAL INTEREST

The authors declare that they have no competing financial interests.

Figures

Figure 1
Figure 1
A schematic representation of the I-TASSER protocol for protein structure and function predictions. The protein chains are colored from blue at N-terminus to red at the C-terminus.
Figure 2
Figure 2
Example of external restraint files that users can use to specify (a) residue-residue contact/distance restraints; (b) query-template alignment in FASTA format; and (c) query-template alignment in 3D format.
Figure 3
Figure 3
An illustrative example of the I-TASSER result page showing (a) query sequence in FASTA format and a link to the user-specified restraints; (b) predicted secondary structure of the query protein; and (c) image of the top-five predicted models and links for downloading the PDB formatted structure files. The confidence score for estimating the model quality is reported as C-score. The secondary structures in the model are highlighted in red (for α-helices) and yellow (for β-strands).
Figure 4
Figure 4
An illustrative example of the I-TASSER result page showing (a) top ten threading templates and the alignments for the query protein identified by LOMETS; and (b) structural analogs and their alignment with the I-TASSER model, as identified by TM-align from the PDB library. The quality of the threading alignment in (a) is evaluated based on their normalized Z-score (highlighted in orange), where a normalized Z-score >1 reflects a good alignment. The ranking of the analogs shown in (b) is based on the TM-score (highlighted in green) of the structural alignment.
Figure 5
Figure 5
Illustrative examples of the I-TASSER function predictions on (a) Enzyme Commission numbers; (b) Gene Ontology terms; and (c) ligand-binding sites. The confidence level of the function prediction on EC number and binding site is shown in EC-score and BS-score columns (highlighted in red and blue rectangles, respectively). For GO, the analogs are first sorted based on Fh-score (in orange rectangle) and then a consensus of the predictions is derived from the top-scoring analogs and the confidence score of the GO prediction is defined as the ‘GO-score’ shown in green. The image in (c) shows the top-scoring binding site prediction in 3D model along with the bound ligand (in magenta), where the binding residues in protein are shown as transparent green spheres. The N- and C-terminus residues are marked by blue and red spheres, respectively.

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