<p>This is a common Q.</p>
<p>Briefly, you have some techniques here that get used separately or combined:</p>
<ul>
<li>Ab initio: assemble the protein from scratch, often via a library fragmented peptides (3-mer, 6-mers, 9-mers) based on real structures.</li>
<li>Template threading: given a protein structure alter it to make it like a give sequence. SWISS-MODEL, Rosetta's SimpleThreadingMover, ModBase, Phyre template threading etc. This is why some of these keep ligands and deal well with multimers. For missing loops in the template these are filled by ab initio methods.</li>
<li>Hybridisation: give a bunch of models mix and match them for the best energy. I-Tasser, RosettaCM (which uses SimpleThreadingMover), Phyre (which uses Phyre template threading)</li>
<li>Ab initio with contraints, such as evolutionary covariance. EVFold, AlphaFold2, trRosetta. Often mixed with template based approaches.</li>
</ul>
<p>Wikipedia has more, but papers are very helpful despite the car-salesmanship.</p>
<p>One thing to note is that protein can adopt different conformations. The AlphaFold2/ColabFold notebooks give multiple models: these may be legit alt conformations, e.g. inactive vs active etc etc</p>
<p>Here is a SwissModel vs AF2:
<a href="https://bioinformatics.stackexchange.com/questions/17854/different-structures-of-same-protein-from-two-softwares/17857#17857">Different structures of same protein from two softwares</a></p>
<p>Other helpful As:</p>
<ul>
<li><p><a href="https://bioinformatics.stackexchange.com/questions/16169/how-to-make-3d-model-of-a-protein-that-not-exist-in-pdb/16170#16170">How to make 3d model of a protein that not exist in PDB?</a></p>
</li>
<li><p><a href="https://bioinformatics.stackexchange.com/questions/159/phyre2-vs-itasser-completely-different-models-generated">Phyre2 vs ITasser, completely different models generated</a></p>
</li>
<li><p><a href="https://bioinformatics.stackexchange.com/questions/18894/how-reliable-is-alphafold2-for-folding-random-coil-peptide">How reliable is Alphafold2 for folding random-coil peptide</a> —discussion of technical details going wrong... Personally, I had Phyre2 made an alignment mistake which altered the protein</p>
</li>
</ul>

CC BY-SA 4.0
2022-04-22T09:30:59.667Z
2022-04-22T09:30:59.667Z
Matteo Ferla
<p>What is the difference between the I-TASSER, phyre2, and SWISS-model in the 3D tertiary structure?</p>
<p>How do they get the results? When I did a prediction, I got a similar result for the highest template in I-TASSER and Swiss, while it was different with Phyre2. What does that mean?</p>

<phylogenetics><proteins><protein-structure><sequence-analysis><3d-structure>
What is the different between the I-TASSER, phyre2, SWISS-model in the 3D tertiary structure?
# What is the different between the I-TASSER, phyre2, SWISS-model in the 3D tertiary structure?

(Asked by: username_0 on 2022-04-22)

What is the difference between the I-TASSER, phyre2, and SWISS-model in the 3D tertiary structure?

How do they get the results? When I did a prediction, I got a similar result for the highest template in I-TASSER and Swiss, while it was different with Phyre2. What does that mean?

**Tags:** phylogenetics, proteins, protein-structure, sequence-analysis, 3d-structure

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## 1 answers

### Answer by username_1 on 2022-04-22. Score: 2

This is a common Q.

Briefly, you have some techniques here that get used separately or combined:

* Ab initio: assemble the protein from scratch, often via a library fragmented peptides (3-mer, 6-mers, 9-mers) based on real structures.
* Template threading: given a protein structure alter it to make it like a give sequence. SWISS-MODEL, Rosetta's SimpleThreadingMover, ModBase, Phyre template threading etc. This is why some of these keep ligands and deal well with multimers. For missing loops in the template these are filled by ab initio methods.
* Hybridisation: give a bunch of models mix and match them for the best energy. I-Tasser, RosettaCM (which uses SimpleThreadingMover), Phyre (which uses Phyre template threading)
* Ab initio with contraints, such as evolutionary covariance. EVFold, AlphaFold2, trRosetta. Often mixed with template based approaches.

Wikipedia has more, but papers are very helpful despite the car-salesmanship.

One thing to note is that protein can adopt different conformations. The AlphaFold2/ColabFold notebooks give multiple models: these may be legit alt conformations, e.g. inactive vs active etc etc

Here is a SwissModel vs AF2:
[Different structures of same protein from two softwares](https://bioinformatics.stackexchange.com/questions/17854/different-structures-of-same-protein-from-two-softwares/17857#17857)

Other helpful As:

* [How to make 3d model of a protein that not exist in PDB?](https://bioinformatics.stackexchange.com/questions/16169/how-to-make-3d-model-of-a-protein-that-not-exist-in-pdb/16170#16170)
* [Phyre2 vs ITasser, completely different models generated](https://bioinformatics.stackexchange.com/questions/159/phyre2-vs-itasser-completely-different-models-generated)
* [How reliable is Alphafold2 for folding random-coil peptide](https://bioinformatics.stackexchange.com/questions/18894/how-reliable-is-alphafold2-for-folding-random-coil-peptide) —discussion of technical details going wrong... Personally, I had Phyre2 made an alignment mistake which altered the protein


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