I-TASSER Server: New Development for Protein Structure and Function Predictions

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2015 Apr 18

PMID 25883148

Citations 1097

Authors

Jianyi Yang

Yang Zhang

Affiliations

Soon will be listed here.

Abstract

The I-TASSER server (http://zhanglab.ccmb.med.umich.edu/I-TASSER) is an online resource for automated protein structure prediction and structure-based function annotation. In I-TASSER, structural templates are first recognized from the PDB using multiple threading alignment approaches. Full-length structure models are then constructed by iterative fragment assembly simulations. The functional insights are finally derived by matching the predicted structure models with known proteins in the function databases. Although the server has been widely used for various biological and biomedical investigations, numerous comments and suggestions have been reported from the user community. In this article, we summarize recent developments on the I-TASSER server, which were designed to address the requirements from the user community and to increase the accuracy of modeling predictions. Focuses have been made on the introduction of new methods for atomic-level structure refinement, local structure quality estimation and biological function annotations. We expect that these new developments will improve the quality of the I-TASSER server and further facilitate its use by the community for high-resolution structure and function prediction.

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References

Yang J, Roy A, Zhang Y . BioLiP: a semi-manually curated database for biologically relevant ligand-protein interactions. Nucleic Acids Res. 2012; 41(Database issue):D1096-103. PMC: 3531193. DOI: 10.1093/nar/gks966. View

Wu S, Zhang Y . LOMETS: a local meta-threading-server for protein structure prediction. Nucleic Acids Res. 2007; 35(10):3375-82. PMC: 1904280. DOI: 10.1093/nar/gkm251. View

Berman H, Westbrook J, Feng Z, Gilliland G, Bhat T, Weissig H . The Protein Data Bank. Nucleic Acids Res. 1999; 28(1):235-42. PMC: 102472. DOI: 10.1093/nar/28.1.235. View

Brylinski M, Skolnick J . A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation. Proc Natl Acad Sci U S A. 2008; 105(1):129-34. PMC: 2224172. DOI: 10.1073/pnas.0707684105. View

Xu D, Zhang Y . Improving the physical realism and structural accuracy of protein models by a two-step atomic-level energy minimization. Biophys J. 2011; 101(10):2525-34. PMC: 3218324. DOI: 10.1016/j.bpj.2011.10.024. View

Wass M, Kelley L, Sternberg M . 3DLigandSite: predicting ligand-binding sites using similar structures. Nucleic Acids Res. 2010; 38(Web Server issue):W469-73. PMC: 2896164. DOI: 10.1093/nar/gkq406. View

Zhang Y, Skolnick J . Scoring function for automated assessment of protein structure template quality. Proteins. 2004; 57(4):702-10. DOI: 10.1002/prot.20264. View

Zhang Y, Skolnick J . TM-align: a protein structure alignment algorithm based on the TM-score. Nucleic Acids Res. 2005; 33(7):2302-9. PMC: 1084323. DOI: 10.1093/nar/gki524. View

Battey J, Kopp J, Bordoli L, Read R, Clarke N, Schwede T . Automated server predictions in CASP7. Proteins. 2007; 69 Suppl 8:68-82. DOI: 10.1002/prot.21761. View

10.

Zhang Y, Kolinski A, Skolnick J . TOUCHSTONE II: a new approach to ab initio protein structure prediction. Biophys J. 2003; 85(2):1145-64. PMC: 1303233. DOI: 10.1016/S0006-3495(03)74551-2. View

11.

Huang Y, Mao B, Aramini J, Montelione G . Assessment of template-based protein structure predictions in CASP10. Proteins. 2013; 82 Suppl 2:43-56. PMC: 3932189. DOI: 10.1002/prot.24488. View

12.

Haas J, Roth S, Arnold K, Kiefer F, Schmidt T, Bordoli L . The Protein Model Portal--a comprehensive resource for protein structure and model information. Database (Oxford). 2013; 2013:bat031. PMC: 3889916. DOI: 10.1093/database/bat031. View

13.

Zhang Y, Skolnick J . SPICKER: a clustering approach to identify near-native protein folds. J Comput Chem. 2004; 25(6):865-71. DOI: 10.1002/jcc.20011. View

14.

Zhang Y . Interplay of I-TASSER and QUARK for template-based and ab initio protein structure prediction in CASP10. Proteins. 2013; 82 Suppl 2:175-87. PMC: 4067246. DOI: 10.1002/prot.24341. View

15.

Roy A, Yang J, Zhang Y . COFACTOR: an accurate comparative algorithm for structure-based protein function annotation. Nucleic Acids Res. 2012; 40(Web Server issue):W471-7. PMC: 3394312. DOI: 10.1093/nar/gks372. View

16.

Zhang Y . Protein structure prediction: when is it useful?. Curr Opin Struct Biol. 2009; 19(2):145-55. PMC: 2673339. DOI: 10.1016/j.sbi.2009.02.005. View

17.

Roy A, Kucukural A, Zhang Y . I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc. 2010; 5(4):725-38. PMC: 2849174. DOI: 10.1038/nprot.2010.5. View

18.

Moult J, Fidelis K, Kryshtafovych A, Schwede T, Tramontano A . Critical assessment of methods of protein structure prediction (CASP)--round x. Proteins. 2013; 82 Suppl 2:1-6. PMC: 4394854. DOI: 10.1002/prot.24452. View

19.

Zhang J, Liang Y, Zhang Y . Atomic-level protein structure refinement using fragment-guided molecular dynamics conformation sampling. Structure. 2011; 19(12):1784-95. PMC: 3240822. DOI: 10.1016/j.str.2011.09.022. View

20.

Yang J, Roy A, Zhang Y . Protein-ligand binding site recognition using complementary binding-specific substructure comparison and sequence profile alignment. Bioinformatics. 2013; 29(20):2588-95. PMC: 3789548. DOI: 10.1093/bioinformatics/btt447. View