text: user15378: 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?
  
  user6322: 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
  Other helpful As:
  
  How to make 3d model of a protein that not exist in PDB?
  
  Phyre2 vs ITasser, completely different models generated
  
  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
  
  
  
original_text: 15378: <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>
   6322: <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>
  