Answers.Body: <p>OK, trying to answer question 2, think I need to be sure that both enzymes have same identical heme cofactor and then find a rotation/translation matrix that applied to heme of protein A moved exactly on top of heme of protein B , than I have to move the entire protein backbone of protein A using that matrix, is it reasonable ? Am I getting it wrong ? With <strong>PyMOL</strong> I tried to use <code>Pair/Pair_fit</code> command with two heme proteins :
  <code>2d0t</code> <a href="https://www.rcsb.org/structure/2d0t" rel="nofollow noreferrer">https://www.rcsb.org/structure/2d0t</a> and <code>4zv8</code> (<a href="https://www.rcsb.org/structure/4ZV8" rel="nofollow noreferrer">https://www.rcsb.org/structure/4ZV8</a>) :</p>
  <p><code>pair hem_2d0t , hem_4zv8,</code>  same as <code>pair_fit hem_2d0t , hem_4zv8</code>, where <code>hem_2d0t</code>,<code>hem_4zv8</code>  are the heme of the two proteins [<code>select model 2d0t and resn HEM</code> and <code>set_name sele, hem_2d0t</code> or <code>select hem_2d0t, model 2d0t and resn HEM</code>].</p>
  <p>See results, superposed heme:</p>
  <p><a href="https://i.sstatic.net/IVUTq.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/IVUTq.png" alt="enter image description here" /></a></p>
  <p>Superposed Proteins :</p>
  <p><a href="https://i.sstatic.net/uAsRi.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/uAsRi.png" alt="enter image description here" /></a></p>
  <p>As for question 1 I tried to answer using the tools available to me.
  I picked the two same proteins : <code>2d0t</code> (<a href="https://i.sstatic.net/IVUTq.png" rel="nofollow noreferrer">https://www.rcsb.org/structure/2d0t</a> and <code>4zv8</code> (<a href="https://i.sstatic.net/uAsRi.png" rel="nofollow noreferrer">https://www.rcsb.org/structure/4ZV8</a>). Using <code>parKVFinder</code> (<a href="https://i.sstatic.net/qqzr4.png" rel="nofollow noreferrer">https://github.com/LBC-LNBio/parKVFinder</a> , <a href="https://i.sstatic.net/73rfc.png" rel="nofollow noreferrer">https://www.softxjournal.com/article/S2352-7110(20)30319-8/fulltext</a>) <strong>pymol plugin</strong> on both proteins stripped of all their HETATM, I calculated their cavities. As an example , here a png of <code>2d0t</code>  cavities :</p>
  <p><a href="https://i.sstatic.net/qqzr4.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/qqzr4.png" alt="enter image description here" /></a></p>
  <p>Then I extracted the residues surrounding the cavity using :</p>
  <p><code>select model 2d0t_merged near_to 5.0 of resn KAF</code> ; [named <code>sele_2d0t</code>]</p>
  <p><code>select model 4zv8_merged near_to 5.0 of resn KAB</code> ; [named <code>sele_4zv8</code>]</p>
  <p>being <code>KAF</code> and <code>KAB</code> cavities described as non_bounded atom in pdb format as output of <code>parKVFinder</code> .<br />
  I believe <code>parKVFinder</code> has its own output for the residues surrounding cavities, but wanted to try <code>PyMOL</code></p>
  <p>Example for <code>2d0t</code> :</p>
  <p><a href="https://i.sstatic.net/73rfc.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/73rfc.png" alt="enter image description here" /></a></p>
  <p>Then I used</p>
  <p><code>cealign sele_4zv8 , sele_2d0t</code> (<a href="https://pymolwiki.org/index.php/Cealign" rel="nofollow noreferrer">https://pymolwiki.org/index.php/Cealign</a>) to align the residues of the two cavities. (<code>cealign</code> uses just CA of the selections provided).</p>
  <p>Results , only cavities and surrounding residues :</p>
  <p><a href="https://i.sstatic.net/aIEa5.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/aIEa5.png" alt="enter image description here" /></a></p>
  <p>the two heme protein cavities are not alignrd even if the HIS (2dt0, red)  and CYS (4zv8, yellow) are on the same side :</p>
  <p><a href="https://i.sstatic.net/knQt2.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/knQt2.png" alt="enter image description here" /></a></p>
  <p>NOTE:</p>
  <p>2dt0 in magenta</p>
  <p>4zv8 in cyan</p>
  <p>I choose 2 different heme protein (could be more extreme though) , just because the question was open to broad attempts, could be interesting too see for example results on not too distant cytochromes</p>
  
Answers.ContentLicense: CC BY-SA 4.0
Answers.CreationDate: 2023-10-02T16:02:41.570Z
Answers.Text: Thank you very much. I will try to follow the process and report back.
Answers.UserDisplayName: Irfan
Answers.ContentLicense: CC BY-SA 4.0
Answers.CreationDate: 2023-09-28T20:32:57.607Z
Answers.LastActivityDate: 2024-05-25T08:04:47.257Z
Answers.LastEditDate: 2024-05-25T08:04:47.257Z
Answers.UserDisplayName: pippo1980
Body: <p>I have two enzymes, with heme cofactors. but their overall structure is very different.</p>
  <p>I use Pymol regularly to visualize protein pdb structures.</p>
  <p>I want to align both structures, but the structures don't align well due to very low homology. However, their active sites/substrate entrance channels may be more similar than the rest of the structure.
  so,</p>
  <ol>
  <li>I want to align only the substrate channels from both enzymes and compare their structure.
  or</li>
  <li>align both proteins only using the heme as a reference point. So both hemes from two enzymes align and then I can manually do the rest.</li>
  </ol>
  <p>I am more interested in how the substrate would be accessible in both enzymes differently.</p>
  <p>Thanks in advance.</p>
  <p>Edit: Sorry for being a bit unclear. We can pick two proteins like cytochrome P450 BM3 with pdb id 6H1L or 6H1O. The second protein can be a similar peroxygenase UPO, e.g. 7pn4.
  Thanks.</p>
  
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2023-09-27T09:26:18.827Z
Comments.Text: @terdon , do the same rules of SO apply to Bioinformatics , the question seems too wide , at least irfan could have named two pdbs code as inputs, toghrther with the aa defining the channels  to have us to try to get a result with
Comments.UserDisplayName: pippo1980
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2023-09-27T09:33:53.900Z
Comments.Text: If you feel the question is too broad, then ask for clarifications and/or vote to close as "needs more focus". That said, I don't see why this is too broad: the main question here is "given two pdb structures, how can I align and compare only specific parts of those structures instead?" which seems like it should be answerable by those working with this kind of data.
Comments.UserDisplayName: terdon
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2023-09-28T03:13:40.247Z
Comments.Text: Please add more context to this question; be as specific as possible about the problem you're struggling with. Example proteins, or other input files, are very helpful.
Comments.UserDisplayName: gringer
Tags: <pdb><pymol>
Title: Align two different structures with respect to their active sites or heme cofactor
ThreadText: # Align two different structures with respect to their active sites or heme cofactor
  
  (Asked by: username_0 on 2023-09-27)
  
  I have two enzymes, with heme cofactors. but their overall structure is very different.
  
  I use Pymol regularly to visualize protein pdb structures.
  
  I want to align both structures, but the structures don't align well due to very low homology. However, their active sites/substrate entrance channels may be more similar than the rest of the structure.
  so,
  
  1. I want to align only the substrate channels from both enzymes and compare their structure.
     or
  2. align both proteins only using the heme as a reference point. So both hemes from two enzymes align and then I can manually do the rest.
  
  I am more interested in how the substrate would be accessible in both enzymes differently.
  
  Thanks in advance.
  
  Edit: Sorry for being a bit unclear. We can pick two proteins like cytochrome P450 BM3 with pdb id 6H1L or 6H1O. The second protein can be a similar peroxygenase UPO, e.g. 7pn4.
  Thanks.
  
  **Tags:** pdb, pymol
  
  > **Comments:**
  > **username_1**: @username_2 , do the same rules of SO apply to Bioinformatics , the question seems too wide , at least username_0 could have named two pdbs code as inputs, toghrther with the aa defining the channels  to have us to try to get a result with  
  > **username_2**: If you feel the question is too broad, then ask for clarifications and/or vote to close as "needs more focus". That said, I don't see why this is too broad: the main question here is "given two pdb structures, how can I align and compare only specific parts of those structures instead?" which seems like it should be answerable by those working with this kind of data.  
  > **username_3**: Please add more context to this question; be as specific as possible about the problem you're struggling with. Example proteins, or other input files, are very helpful.  
  
  ---
  
  ## 1 answers
  
  ### Answer by username_1 on 2023-09-28. Score: 1
  
  OK, trying to answer question 2, think I need to be sure that both enzymes have same identical heme cofactor and then find a rotation/translation matrix that applied to heme of protein A moved exactly on top of heme of protein B , than I have to move the entire protein backbone of protein A using that matrix, is it reasonable ? Am I getting it wrong ? With **PyMOL** I tried to use `Pair/Pair_fit` command with two heme proteins :
  `2d0t` <https://www.rcsb.org/structure/2d0t> and `4zv8` (<https://www.rcsb.org/structure/4ZV8>) :
  
  `pair hem_2d0t , hem_4zv8,` same as `pair_fit hem_2d0t , hem_4zv8`, where `hem_2d0t`,`hem_4zv8` are the heme of the two proteins [`select model 2d0t and resn HEM` and `set_name sele, hem_2d0t` or `select hem_2d0t, model 2d0t and resn HEM`].
  
  See results, superposed heme:
  
  [![enter image description here](https://i.sstatic.net/IVUTq.png)](https://i.sstatic.net/IVUTq.png)
  
  Superposed Proteins :
  
  [![enter image description here](https://i.sstatic.net/uAsRi.png)](https://i.sstatic.net/uAsRi.png)
  
  As for question 1 I tried to answer using the tools available to me.
  I picked the two same proteins : `2d0t` ([https://www.rcsb.org/structure/2d0t](https://i.sstatic.net/IVUTq.png) and `4zv8` ([https://www.rcsb.org/structure/4ZV8](https://i.sstatic.net/uAsRi.png)). Using `parKVFinder` ([https://github.com/LBC-LNBio/parKVFinder](https://i.sstatic.net/qqzr4.png) , [https://www.softxjournal.com/article/S2352-7110(20)30319-8/fulltext](https://i.sstatic.net/73rfc.png)) **pymol plugin** on both proteins stripped of all their HETATM, I calculated their cavities. As an example , here a png of `2d0t` cavities :
  
  [![enter image description here](https://i.sstatic.net/qqzr4.png)](https://i.sstatic.net/qqzr4.png)
  
  Then I extracted the residues surrounding the cavity using :
  
  `select model 2d0t_merged near_to 5.0 of resn KAF` ; [named `sele_2d0t`]
  
  `select model 4zv8_merged near_to 5.0 of resn KAB` ; [named `sele_4zv8`]
  
  being `KAF` and `KAB` cavities described as non\_bounded atom in pdb format as output of `parKVFinder` .  
  I believe `parKVFinder` has its own output for the residues surrounding cavities, but wanted to try `PyMOL`
  
  Example for `2d0t` :
  
  [![enter image description here](https://i.sstatic.net/73rfc.png)](https://i.sstatic.net/73rfc.png)
  
  Then I used
  
  `cealign sele_4zv8 , sele_2d0t` (<https://pymolwiki.org/index.php/Cealign>) to align the residues of the two cavities. (`cealign` uses just CA of the selections provided).
  
  Results , only cavities and surrounding residues :
  
  [![enter image description here](https://i.sstatic.net/aIEa5.png)](https://i.sstatic.net/aIEa5.png)
  
  the two heme protein cavities are not alignrd even if the HIS (2dt0, red) and CYS (4zv8, yellow) are on the same side :
  
  [![enter image description here](https://i.sstatic.net/knQt2.png)](https://i.sstatic.net/knQt2.png)
  
  NOTE:
  
  2dt0 in magenta
  
  4zv8 in cyan
  
  I choose 2 different heme protein (could be more extreme though) , just because the question was open to broad attempts, could be interesting too see for example results on not too distant cytochromes
  
  > **Comments:**
  > **username_0**: Thank you very much. I will try to follow the process and report back.  
  
  ---
  
  