Practical Guide to Homology Modeling: Difference between revisions
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<table style="background:#ffff80;"><tr><td>Many assertions in this article are lacking literature citations. Help improving documentation in this article will be appreciated. Wikipedia's article on [http://en.wikipedia.org/wiki/Homology_modeling Homology modeling] is well documented, although more technical and less of a practical guide than the present article.</td></tr></table> | <table style="background:#ffff80;"><tr><td> | ||
<big>Homology modeling has become largely obsolete since the 2020 success of structure prediction by [[AlphaFold]] and other AI prediction systems. Rather than starting here, we suggest starting at [[How To Find A Structure]]. | |||
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Many assertions in this article are lacking literature citations. Help improving documentation in this article will be appreciated. Wikipedia's article on [http://en.wikipedia.org/wiki/Homology_modeling Homology modeling] is well documented, although more technical and less of a practical guide than the present article.</td></tr></table> | |||
== Terminology == | == Terminology == | ||
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You don’t need a homology model if the amino acid sequence of interest (the query sequence) already has an empirically determined 3D structure. Structures determined empirically, by X-ray crystallography or (much less often) by solution NMR or cryo-EM, will almost always be more accurate than a homology model. | You don’t need a homology model if the amino acid sequence of interest (the query sequence) already has an empirically determined 3D structure. Structures determined empirically, by X-ray crystallography or (much less often) by solution NMR or cryo-EM, will almost always be more accurate than a homology model. | ||
If [[AlphaFold]] has predicted a model for your amino acid sequence of interest, it will often be more accurate than a homology model, and in most cases, a homology model won't be possible due to lack of a suitable template. | |||
=== Has AlphaFold predicted a model? === | |||
Empirical models are the most reliable, but if none are available, [[AlphaFold]] has an impressive track record of correctly predicting structures from sequence. Check the [http://alphafold.ebi.ac.uk AlphaFold Database] for a model of your protein of interest. You can also submit a sequence and get a prediction: [[How to predict structures with AlphaFold]]. Another model prediction service with a good track record is [http://robetta.bakerlab.org RoseTTaFold]. Submit your sequence there, making sure to check ''RoseTTaFold'' as the method. With any of these methods, download the predicted [[PDB file]] and then upload it to [http://firstglance.jmol.org FirstGlance in Jmol] for exploration and analysis. FirstGlance automatically colors predicted models by reliability. | |||
=== Is there an empirical model? === | === Is there an empirical model? === | ||
All published, empirically-determined, atomic-resolution, macromolecular 3D structures are available in the [[World Wide Protein Data Bank]]. | [[Empirical models|Empirically-determined]] models are usually the most reliable. All published, empirically-determined, atomic-resolution, macromolecular 3D structures are available in the [[World Wide Protein Data Bank]]. | ||
Each model in the PDB has a unique 4-character identification code ([[PDB ID]]) that begins with a numeral, and has letters or numerals for the last 3 characters . Examples are 1d66, 4mdh, 9ins. | Each model in the PDB has a unique 4-character identification code ([[PDB ID]]) that begins with a numeral, and has letters or numerals for the last 3 characters . Examples are 1d66, 4mdh, 9ins. | ||
Here are two methods for finding out if your query amino acid sequence, or parts of it, have empirically-determined 3D structures in the PDB. | Here are two methods for finding out if your query amino acid sequence, or parts of it, have [[Empirical models|empirically-determined 3D structures]] in the PDB. | ||
==== Simple search for empirical models (via PIR) ==== | ==== Simple search for empirical models (via PIR) ==== | ||
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==== FoldIndex ==== | ==== FoldIndex ==== | ||
The [ | The [https://fold.proteopedia.org FoldIndex server] is a useful adjunct to the MobiDB report, since it is not included in that report. | ||
==Is your query protein in the structural genomics pipeline?== | ==Is your query protein in the structural genomics pipeline?== | ||
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*At [http://uniprot.org UniProt.Org], find your sequence, and copy it in FASTA format. | *At [http://uniprot.org UniProt.Org], find your sequence, and copy it in FASTA format. | ||
*Go to [http://swissmodel.expasy.org SwissModel.expasy.org]. | *Go to [http://swissmodel.expasy.org SwissModel.expasy.org]<ref name="promod3">PMID: 33507980</ref>. | ||
*It is a good idea to create an account, and login. This makes it easy to find your models later, although they are not kept on the server more than a week. | *It is a good idea to create an account, and login. This makes it easy to find your models later, although they are not kept on the server more than a week. | ||
