List of protein structure prediction software

Constituent amino-acids can be analyzed to predict secondary, tertiary and quaternary protein structure.

This list of protein structure prediction software summarizes notable used software tools in protein structure prediction, including homology modeling, protein threading, ab initio methods, secondary structure prediction, and transmembrane helix and signal peptide prediction.

Software list

Below is a list which separates programs according to the method used for structure prediction.

Homology modeling

Name MethodDescriptionRelease date Reference
IntFOLD A unified interface for: Tertiary structure prediction/3D modelling, 3D model quality assessment, Intrinsic disorder prediction, Domain prediction, Prediction of protein-ligand binding residues Automated webserver and some downloadable programs 2011 Roche & McGuffin, 2011
RaptorX remote homology detection, protein 3D modeling, binding site predictionAutomated webserver and Downloadable program 2011 Peng & Xu, 2011
Biskit wraps external programs into automated workflowBLAST search, T-Coffee alignment, and MODELLER construction 2007 Grünberg et al., 2007
ESyPred3D Template detection, alignment, 3D modelingAutomated webserver 2002 Lambert et al., 2002
FoldX Energy calculations and protein designDownloadable program 2005 Schymkowitz et al., 2005
Phyre, Phyre2 Remote template detection, alignment, 3D modeling, multi-templates, ab initioWebserver with job manager, automatically updated fold library, genome searching and other facilities 2009 Kelley & Sternberg, 2009
HHpred Template detection, alignment, 3D modelingInteractive webserver with help facility 2005 Söding et al., 2005
MODELLER Satisfaction of spatial restraintsStandalone program mainly in Fortran and Python 1993 Šali & Blundell, 1993
CONFOLD Satisfaction of contact and distance restraintsStandalone program mainly in Fortran and Perl 2015 Adhikari et al., 2015
Molecular Operating Environment (MOE) Template identification, use of multiple templates and accounting for other environments (e.g. excluded ligand volumes), loop modelling, rotamer libraries for sidechain conformations, relaxation using MM forcefields.Proprietary platform, supported on Windows, Linux and Mac 1994 Chemical Computing Group; MOE documentation
Robetta Rosetta homology modeling and ab initio fragment assembly with Ginzu domain predictionWebserver 2004 Kim et al., 2004
BHAGEERATH-H Combination of ab initio folding and homology methodsProtein tertiary structure predictions 2014 Jayaram et al., 2014
Swiss-model Local similarity/fragment assemblyAutomated webserver (based on ProModII) 1993 Peitsch et al.; SWISS-MODEL documentation
Yasara Detection of templates, alignment, modeling incl. ligands and oligomers, hybridization of model fragmentsGraphical interface or text mode (clusters) 2003 YASARA development history/documentation
AWSEM-Suite Molecular dynamics simulation based on template-guided, coevolutionary-enhanced optimized folding landscapesAutomated webserver 2020 Jin et al., 2020
ModPipe Automated comparative modeling; MODELLER-based Automated pipeline for large-scale comparative protein structure modeling using sequence–structure relationships and MODELLER-based model generation 2003 Eswar et al., 2003
ModWeb Automated comparative modeling Web-based automated comparative-modeling server that uses sequence searches, template selection, alignment and MODELLER for protein structure modeling 2003 Eswar et al.; ModWeb documentation
CPHmodels Homology modeling / fragment assembly Automated server for protein homology modeling using template identification, sequence–structure alignment and model construction 2003 Nielsen et al., 2003
3D-JIGSAW Comparative modeling / rigid-body assembly Automated protein comparative-modeling server that identifies structural templates and assembles models from conserved structural regions 2001 Bates et al., 2001
M4T Multiple-template comparative modeling Comparative-modeling server that combines multiple templates with iterative optimization of alternative target–template alignments 2005 Fernandez-Fuentes et al., 2005
ICM Template-based comparative modeling Molecular-modeling platform supporting protein homology modeling, template selection, alignment, loop modeling and structure refinement 1994 Abagyan et al. 2012; comparative modeling evaluations
Prime Comparative/homology modeling Protein-structure modeling module using template-based modeling, loop prediction and structural refinement 2006 Comparative modeling evaluation
COMPOSER Rigid-body comparative modeling Classical comparative-modeling program that constructs protein models through rigid-body assembly of conserved structural regions 1987 Sutcliffe et al., 1987; comparative-modeling literature
PrISM Comparative modeling / structural alignment Protein modeling system that uses structural templates and sequence–structure relationships for comparative model construction. 2000 Yang & Honig; comparative-modeling literature
Geno3D Homology modeling / segment matching Web-based protein structure-prediction server that uses comparative modeling and structural template information to construct three-dimensional models. Combet et al., 2005

Threading and fold recognition

Name MethodDescriptionRelease date Reference
IntFOLD A unified interface for: Tertiary structure prediction/3D modelling, 3D model quality assessment, Intrinsic disorder prediction, Domain prediction, Prediction of protein-ligand binding residues Automated webserver and some downloadable programs 2011 Roche et al. (2011)
RaptorX Remote template detection, single-template and multi-template threading, totally different from and much better than the old program RAPTOR designed by the same groupWebserver with job manager, automatically updated fold library 2011 Peng & Xu (2011)
HHpred Template detection, alignment, 3D modelingInteractive webserver with help facility 2005 Söding, Biegert & Lupas (2005)
Phyre, Phyre2 Remote template detection, alignment, 3D modeling, multi-templates, ab initioWebserver with job manager, automatically updated fold library, genome searching and other facilities 2009 Kelley & Sternberg (2009)
I-TASSER Threading fragment structure reassembly On-line server for protein modeling https://zhanggroup.org/I-TASSER/ 2008 Zhang (2008)

Ab initio structure prediction

Name MethodDescriptionRelease date Reference
trRosetta trRosetta is an algorithm for fast and accurate protein structure prediction. It supports single-sequence structure prediction with trRosettaX-Single.Webserver and source codes available at: https://yanglab.qd.sdu.edu.cn/trRosetta/ 2020 Yang et al. (2020)
ROBETTA Rosetta homology modeling and ab initio fragment assembly with Ginzu domain predictionWebserver 2004 Kim, Chivian & Baker (2004)
Rosetta@home Distributed-computing implementation of Rosetta algorithmDownloadable program 2005 Rosetta Commons timeline; Rosetta@home documentation
Abalone Molecular Dynamics foldingProgram 2006 Abalone software documentation
C-QUARK C-QUARK is a method for ab initio protein structure prediction. Based on deep-learning based contact-map predictions into the fragment assembly simulations. Webserver https://zhanggroup.org/C-QUARK/ 2021 Zheng et al. (2021)
AlphaFold2 An end-to-end deep learning framework for protein structure prediction Webserver and downloadable program 2021 Jumper et al. (2021)
D-I-TASSER The deep learning-based I-TASSER program reportedly outperforms both AlphaFold2 and AlphaFold3 Webserver https://zhanggroup.org/D-I-TASSER/ 2023 Zheng et al. (2023)

Secondary structure prediction

Detailed list of programs can be found at List of protein secondary structure prediction programs

See also

References

  1. ↑ Roche, Daniel B.; Buenavista, Maria T.; Tetchner, Stuart J.; McGuffin, Liam J. (2011-07-01). "The IntFOLD server: an integrated web resource for protein fold recognition, 3D model quality assessment, intrinsic disorder prediction, domain prediction and ligand binding site prediction". Nucleic Acids Research. 39 (suppl_2): W171–W176. doi:10.1093/nar/gkr184. ISSN 0305-1048. PMC 3125722. PMID 21459847.
  2. ↑ Peng, Jian; Xu, Jinbo (2011). "Raptorx: Exploiting structure information for protein alignment by statistical inference". Proteins: Structure, Function, and Bioinformatics. 79 (S10): 161–171. doi:10.1002/prot.23175. ISSN 1097-0134. PMC 3226909. PMID 21987485.
  3. ↑ Grünberg, Raik; Nilges, Michael; Leckner, Johan (2007-03-01). "Biskit—A software platform for structural bioinformatics". Bioinformatics. 23 (6): 769–770. doi:10.1093/bioinformatics/btl655. ISSN 1367-4803. PMID 17237072.
  4. ↑ Lambert, Christophe; Léonard, Nadia; De Bolle, Xavier; Depiereux, Eric (2002-09-01). "ESyPred3D: Prediction of proteins 3D structures". Bioinformatics. 18 (9): 1250–1256. doi:10.1093/bioinformatics/18.9.1250. ISSN 1367-4803. PMID 12217917.
  5. ↑ Schymkowitz, Joost; Borg, Jesper; Stricher, Francois; Nys, Robby; Rousseau, Frederic; Serrano, Luis (2005-07-01). "The FoldX web server: an online force field". Nucleic Acids Research. 33 (suppl_2): W382–W388. doi:10.1093/nar/gki387. ISSN 0305-1048. PMC 1160148. PMID 15980494.
  6. ↑ Kelley, Lawrence A.; Sternberg, Michael J. E. (March 2009). "Protein structure prediction on the Web: a case study using the Phyre server". Nature Protocols. 4 (3). Nature Publishing Group: 363–371. doi:10.1038/nprot.2009.2. ISSN 1750-2799. PMID 19247286.
  7. ↑ Söding, Johannes; Biegert, Andreas; Lupas, Andrei N. (2005-07-01). "The HHpred interactive server for protein homology detection and structure prediction". Nucleic Acids Research. 33 (suppl_2): W244–W248. doi:10.1093/nar/gki408. ISSN 0305-1048. PMC 1160169. PMID 15980461.
  8. ↑ Webb, Benjamin; Sali, Andrej (2016). "Comparative Protein Structure Modeling Using MODELLER". Current Protocols in Bioinformatics. 54 (1): 5.6.1–5.6.37. doi:10.1002/cpbi.3. ISSN 1934-340X. PMC 5031415. PMID 27322406.
  9. ↑ Adhikari, Badri; Bhattacharya, Debswapna; Cao, Renzhi; Cheng, Jianlin (August 2015). "CONFOLD: Residue-residue contact-guided ab initio protein folding: Contact-Guided Protein Folding". Proteins: Structure, Function, and Bioinformatics. 83 (8): 1436–1449. doi:10.1002/prot.24829. PMC 4509844. PMID 25974172.
  10. ↑ Kim, David E.; Chivian, Dylan; Baker, David (2004-07-01). "Protein structure prediction and analysis using the Robetta server". Nucleic Acids Research. 32 (suppl_2): W526–W531. doi:10.1093/nar/gkh468. ISSN 0305-1048. PMC 441606. PMID 15215442.
  11. ↑ Jayaram, B.; Dhingra, Priyanka; Mishra, Avinash; Kaushik, Rahul; Mukherjee, Goutam; Singh, Ankita; Shekhar, Shashank (2014-12-08). "Bhageerath-H: A homology/ab initio hybrid server for predicting tertiary structures of monomeric soluble proteins". BMC Bioinformatics. 15 (16): S7. doi:10.1186/1471-2105-15-S16-S7. ISSN 1471-2105. PMC 4290660. PMID 25521245.
  12. ↑ Schwede, Torsten; Kopp, Jürgen; Guex, Nicolas; Peitsch, Manuel C. (2003-07-01). "SWISS-MODEL: an automated protein homology-modeling server". Nucleic Acids Research. 31 (13): 3381–3385. doi:10.1093/nar/gkg520. ISSN 0305-1048. PMC 168927. PMID 12824332.
  13. ↑ "YASARA - Yet Another Scientific Artificial Reality Application". www.yasara.org. Retrieved 2026-09-14.
  14. ↑ Jin, Shikai; Contessoto, Vinicius G; Chen, Mingchen; Schafer, Nicholas P; Lu, Wei; Chen, Xun; Bueno, Carlos; Hajitaheri, Arya; Sirovetz, Brian J; Davtyan, Aram; Papoian, Garegin A; Tsai, Min-Yeh; Wolynes, Peter G (2020-07-02). "AWSEM-Suite: a protein structure prediction server based on template-guided, coevolutionary-enhanced optimized folding landscapes". Nucleic Acids Research. 48 (W1): W25–W30. doi:10.1093/nar/gkaa356. ISSN 0305-1048. PMC 7319565. PMID 32383764.
  15. ↑ Schwede, Torsten; Kopp, Jürgen; Guex, Nicolas; Peitsch, Manuel C. (2003-07-01). "SWISS-MODEL: an automated protein homology-modeling server". Nucleic Acids Research. 31 (13): 3381–3385. doi:10.1093/nar/gkg520. ISSN 0305-1048. PMC 168927. PMID 12824332.
  16. ↑ "References | SWISS-MODEL". swissmodel.expasy.org. Retrieved 2026-09-14.
  17. ↑ Schwede, Torsten; Kopp, Jürgen; Guex, Nicolas; Peitsch, Manuel C. (2003-07-01). "SWISS-MODEL: an automated protein homology-modeling server". Nucleic Acids Research. 31 (13): 3381–3385. doi:10.1093/nar/gkg520. ISSN 0305-1048. PMC 168927. PMID 12824332.
  18. ↑ Schwede, Torsten; Kopp, Jürgen; Guex, Nicolas; Peitsch, Manuel C. (2003-07-01). "SWISS-MODEL: an automated protein homology-modeling server". Nucleic Acids Research. 31 (13): 3381–3385. doi:10.1093/nar/gkg520. ISSN 0305-1048. PMC 168927. PMID 12824332.
  19. ↑ "Appendix B: Modelling Services | SWISS-MODEL". swissmodel.expasy.org. Retrieved 2026-09-14.
  20. ↑ Dolan, Michael A.; Noah, James W.; Hurt, Darrell (2012), Orry, Andrew J. W.; Abagyan, Ruben (eds.), "Comparison of Common Homology Modeling Algorithms: Application of User-Defined Alignments", Homology Modeling: Methods and Protocols, vol. 857, Totowa, NJ: Humana Press, pp. 399–414, doi:10.1007/978-1-61779-588-6_18, ISBN 978-1-61779-588-6, PMID 22323232, retrieved 2026-09-14{{citation}}: CS1 maint: work parameter with ISBN (link)
  21. ↑ Dolan, Michael A.; Noah, James W.; Hurt, Darrell (2012), Orry, Andrew J. W.; Abagyan, Ruben (eds.), "Comparison of Common Homology Modeling Algorithms: Application of User-Defined Alignments", Homology Modeling: Methods and Protocols, vol. 857, Totowa, NJ: Humana Press, pp. 399–414, doi:10.1007/978-1-61779-588-6_18, ISBN 978-1-61779-588-6, PMID 22323232, retrieved 2026-09-14{{citation}}: CS1 maint: work parameter with ISBN (link)
  22. ↑ Xiang, Zhexin (2012-03-01). "Advances in Homology Protein Structure Modeling". Current Protein & Peptide Science. 7 (3): 217–227. doi:10.2174/138920306777452312. PMC 1839925. PMID 16787261.
  23. ↑ www.salilab.org https://www.salilab.org/publication-archive/Fiser_CompBioChemPhys_2000.pdf?. Retrieved 2026-09-14. {{cite web}}: Missing or empty |title= (help)
  24. ↑ "1. Introduction". paperzz.com. Retrieved 2026-09-14.
  25. ↑ Roche, Daniel B.; Buenavista, Maria T.; Tetchner, Stuart J.; McGuffin, Liam J. (2011-07-01). "The IntFOLD server: an integrated web resource for protein fold recognition, 3D model quality assessment, intrinsic disorder prediction, domain prediction and ligand binding site prediction". Nucleic Acids Research. 39 (suppl_2): W171–W176. doi:10.1093/nar/gkr184. ISSN 0305-1048. PMC 3125722. PMID 21459847.
  26. ↑ Peng, Jian; Xu, Jinbo (2011). "Raptorx: Exploiting structure information for protein alignment by statistical inference". Proteins: Structure, Function, and Bioinformatics. 79 (S10): 161–171. doi:10.1002/prot.23175. ISSN 1097-0134. PMC 3226909. PMID 21987485.
  27. ↑ Söding, Johannes; Biegert, Andreas; Lupas, Andrei N. (2005-07-01). "The HHpred interactive server for protein homology detection and structure prediction". Nucleic Acids Research. 33 (suppl_2): W244–W248. doi:10.1093/nar/gki408. ISSN 0305-1048. PMC 1160169. PMID 15980461.
  28. ↑ Kelley, Lawrence A.; Sternberg, Michael J. E. (March 2009). "Protein structure prediction on the Web: a case study using the Phyre server". Nature Protocols. 4 (3). Nature Publishing Group: 363–371. doi:10.1038/nprot.2009.2. ISSN 1750-2799. PMID 19247286.
  29. ↑ Zhang, Yang (2008-01-23). "I-TASSER server for protein 3D structure prediction". BMC Bioinformatics. 9 (1) 40. doi:10.1186/1471-2105-9-40. ISSN 1471-2105. PMC 2245901. PMID 18215316.
  30. ↑ Du, Zongyang; Su, Hong; Wang, Wenkai; Ye, Lisha; Wei, Hong; Peng, Zhenling; Anishchenko, Ivan; Baker, David; Yang, Jianyi (December 2021). "The trRosetta server for fast and accurate protein structure prediction". Nature Protocols. 16 (12). Nature Publishing Group: 5634–5651. doi:10.1038/s41596-021-00628-9. ISSN 1750-2799. PMID 34759384.
  31. ↑ Kim, David E.; Chivian, Dylan; Baker, David (2004-07-01). "Protein structure prediction and analysis using the Robetta server". Nucleic Acids Research. 32 (suppl_2): W526–W531. doi:10.1093/nar/gkh468. ISSN 0305-1048. PMC 441606. PMID 15215442.
  32. ↑ "Molecular simulations with Abalone-II". www.biomolecular-modeling.com. Retrieved 2026-09-14.
  33. ↑ Mortuza, S. M.; Zheng, Wei; Zhang, Chengxin; Li, Yang; Pearce, Robin; Zhang, Yang (2021-08-18). "Improving fragment-based ab initio protein structure assembly using low-accuracy contact-map predictions". Nature Communications. 12 (1). Nature Publishing Group: 5011. Bibcode:2021NatCo..12.5011M. doi:10.1038/s41467-021-25316-w. ISSN 2041-1723. PMC 8373938. PMID 34408149.
  34. ↑ Jumper, John; Evans, Richard; Pritzel, Alexander; Green, Tim; Figurnov, Michael; Ronneberger, Olaf; Tunyasuvunakool, Kathryn; Bates, Russ; Žídek, Augustin; Potapenko, Anna; Bridgland, Alex; Meyer, Clemens; Kohl, Simon A. A.; Ballard, Andrew J.; Cowie, Andrew (August 2021). "Highly accurate protein structure prediction with AlphaFold". Nature. 596 (7873). Nature Publishing Group: 583–589. Bibcode:2021Natur.596..583J. doi:10.1038/s41586-021-03819-2. ISSN 1476-4687. PMC 8371605. PMID 34265844.
  35. ↑ Zheng, Wei; Wuyun, Qiqige; Freddolino, Lydia; Zhang, Yang (2023). "Integrating deep learning, threading alignments, and a multi-MSA strategy for high-quality protein monomer and complex structure prediction in CASP15". Proteins: Structure, Function, and Bioinformatics. 91 (12): 1684–1703. doi:10.1002/prot.26585. ISSN 1097-0134. PMC 10840719. PMID 37650367.