Placing of a hame-ion centre into an AlfaFold structure
I’d be grateful for any suggestions regarding the following problem/question. Problem Placing of the haem-iron centre in mosquito P450 structure(s) obtained by means of AlfaFold. This is required for follow up docking simulations. There no insect P450 structures deposited in PDB. However, there are numerous mammalian P450 crystal structures some of which are homologous to the mosquito structures I’m dealing with. A distinctive feature of these structures is a haem-iron centre tethered to the protein via a cysteine thiolate ligand. Six regions have been designated as substrate recognition sites (SRS 1-6) based on comparative sequence analysis methods. These SRS are conserved and are thought to participate in the formation of the substrate access channel, and form part of the catalytic site surrounding the haem iron center. My initial approach would be to use Chimera to align the AlfaFold structure against its mammalian homologue PDB structure and assume that the haem-iron centre would be located in the same place. Is there a better way to achieve the same objective?. Your help will be greatly appreciated. Best regards George
Hi George, The approach that you described is the same that I would try. Hopefully the cysteine will be in the right place. Best, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
On Jul 8, 2023, at 3:33 AM, George Tzotzos via Chimera-users <chimera-users@cgl.ucsf.edu> wrote:
I’d be grateful for any suggestions regarding the following problem/question.
Problem Placing of the haem-iron centre in mosquito P450 structure(s) obtained by means of AlfaFold. This is required for follow up docking simulations. There no insect P450 structures deposited in PDB. However, there are numerous mammalian P450 crystal structures some of which are homologous to the mosquito structures I’m dealing with. A distinctive feature of these structures is a haem-iron centre tethered to the protein via a cysteine thiolate ligand. Six regions have been designated as substrate recognition sites (SRS 1-6) based on comparative sequence analysis methods. These SRS are conserved and are thought to participate in the formation of the substrate access channel, and form part of the catalytic site surrounding the haem iron center.
My initial approach would be to use Chimera to align the AlfaFold structure against its mammalian homologue PDB structure and assume that the haem-iron centre would be located in the same place.
Is there a better way to achieve the same objective?.
Your help will be greatly appreciated.
Best regards
George
Thank you Elaine. The problem is that the AlfaFold structures are devoid of side chains. Is there a way to get round this problem? Have a good day George
On 9 Jul 2023, at 17:29, Elaine Meng <meng@cgl.ucsf.edu> wrote:
Hi George, The approach that you described is the same that I would try. Hopefully the cysteine will be in the right place. Best, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
On Jul 8, 2023, at 3:33 AM, George Tzotzos via Chimera-users <chimera-users@cgl.ucsf.edu> wrote:
I’d be grateful for any suggestions regarding the following problem/question.
Problem Placing of the haem-iron centre in mosquito P450 structure(s) obtained by means of AlfaFold. This is required for follow up docking simulations. There no insect P450 structures deposited in PDB. However, there are numerous mammalian P450 crystal structures some of which are homologous to the mosquito structures I’m dealing with. A distinctive feature of these structures is a haem-iron centre tethered to the protein via a cysteine thiolate ligand. Six regions have been designated as substrate recognition sites (SRS 1-6) based on comparative sequence analysis methods. These SRS are conserved and are thought to participate in the formation of the substrate access channel, and form part of the catalytic site surrounding the haem iron center.
My initial approach would be to use Chimera to align the AlfaFold structure against its mammalian homologue PDB structure and assume that the haem-iron centre would be located in the same place.
Is there a better way to achieve the same objective?.
Your help will be greatly appreciated.
Best regards
George
Hi George, I have never heard of this problem. All the AlphaFold models I've ever seen have full side chains. I don't know if you use ChimeraX yet, but it has an interface for searching the AlphaFold database, as well as for predicting (smaller) structures that are not yet in that database. The calculation is not in ChimeraX, however, it is in Google Colab and requires a google account. See: <https://rbvi.ucsf.edu/chimerax/docs/user/tools/alphafold.html> I hope this helps, Best, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
On Jul 10, 2023, at 8:24 AM, George Tzotzos via Chimera-users <chimera-users@cgl.ucsf.edu> wrote:
Thank you Elaine. The problem is that the AlfaFold structures are devoid of side chains. Is there a way to get round this problem?
Have a good day
George
On 9 Jul 2023, at 17:29, Elaine Meng <meng@cgl.ucsf.edu> wrote:
Hi George, The approach that you described is the same that I would try. Hopefully the cysteine will be in the right place. Best, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
On Jul 8, 2023, at 3:33 AM, George Tzotzos via Chimera-users <chimera-users@cgl.ucsf.edu> wrote:
I’d be grateful for any suggestions regarding the following problem/question.
Problem Placing of the haem-iron centre in mosquito P450 structure(s) obtained by means of AlfaFold. This is required for follow up docking simulations. There no insect P450 structures deposited in PDB. However, there are numerous mammalian P450 crystal structures some of which are homologous to the mosquito structures I’m dealing with. A distinctive feature of these structures is a haem-iron centre tethered to the protein via a cysteine thiolate ligand. Six regions have been designated as substrate recognition sites (SRS 1-6) based on comparative sequence analysis methods. These SRS are conserved and are thought to participate in the formation of the substrate access channel, and form part of the catalytic site surrounding the haem iron center.
My initial approach would be to use Chimera to align the AlfaFold structure against its mammalian homologue PDB structure and assume that the haem-iron centre would be located in the same place.
Is there a better way to achieve the same objective?.
Your help will be greatly appreciated.
Best regards
George
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Elaine, Please accept my apologies. I used an AlphaFold structure pretreated to remove the side chains for use in normal mode analysis. It’s getting rather hot in Europe and my brain got tangled up. Thank you once again, and sorry for making a bad use of your time. George
On 10 Jul 2023, at 16:59, Elaine Meng <meng@cgl.ucsf.edu> wrote:
Hi George, I have never heard of this problem. All the AlphaFold models I've ever seen have full side chains.
I don't know if you use ChimeraX yet, but it has an interface for searching the AlphaFold database, as well as for predicting (smaller) structures that are not yet in that database. The calculation is not in ChimeraX, however, it is in Google Colab and requires a google account. See: <https://rbvi.ucsf.edu/chimerax/docs/user/tools/alphafold.html>
I hope this helps, Best, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
On Jul 10, 2023, at 8:24 AM, George Tzotzos via Chimera-users <chimera-users@cgl.ucsf.edu> wrote:
Thank you Elaine. The problem is that the AlfaFold structures are devoid of side chains. Is there a way to get round this problem?
Have a good day
George
On 9 Jul 2023, at 17:29, Elaine Meng <meng@cgl.ucsf.edu> wrote:
Hi George, The approach that you described is the same that I would try. Hopefully the cysteine will be in the right place. Best, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
On Jul 8, 2023, at 3:33 AM, George Tzotzos via Chimera-users <chimera-users@cgl.ucsf.edu> wrote:
I’d be grateful for any suggestions regarding the following problem/question.
Problem Placing of the haem-iron centre in mosquito P450 structure(s) obtained by means of AlfaFold. This is required for follow up docking simulations. There no insect P450 structures deposited in PDB. However, there are numerous mammalian P450 crystal structures some of which are homologous to the mosquito structures I’m dealing with. A distinctive feature of these structures is a haem-iron centre tethered to the protein via a cysteine thiolate ligand. Six regions have been designated as substrate recognition sites (SRS 1-6) based on comparative sequence analysis methods. These SRS are conserved and are thought to participate in the formation of the substrate access channel, and form part of the catalytic site surrounding the haem iron center.
My initial approach would be to use Chimera to align the AlfaFold structure against its mammalian homologue PDB structure and assume that the haem-iron centre would be located in the same place.
Is there a better way to achieve the same objective?.
Your help will be greatly appreciated.
Best regards
George
_______________________________________________ Chimera-users mailing list -- chimera-users@cgl.ucsf.edu: To unsubscribe send an email to chimera-users-leave@cgl.ucsf.edu Manage subscription:
No worries, my own brain is tangled up half of the time, so I totally understand! Best, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
On Jul 10, 2023, at 10:26 AM, George Tzotzos via Chimera-users <chimera-users@cgl.ucsf.edu> wrote:
Elaine,
Please accept my apologies. I used an AlphaFold structure pretreated to remove the side chains for use in normal mode analysis. It’s getting rather hot in Europe and my brain got tangled up.
Thank you once again, and sorry for making a bad use of your time.
George
On 10 Jul 2023, at 16:59, Elaine Meng <meng@cgl.ucsf.edu> wrote:
Hi George, I have never heard of this problem. All the AlphaFold models I've ever seen have full side chains.
I don't know if you use ChimeraX yet, but it has an interface for searching the AlphaFold database, as well as for predicting (smaller) structures that are not yet in that database. The calculation is not in ChimeraX, however, it is in Google Colab and requires a google account. See: <https://rbvi.ucsf.edu/chimerax/docs/user/tools/alphafold.html>
I hope this helps, Best, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
On Jul 10, 2023, at 8:24 AM, George Tzotzos via Chimera-users <chimera-users@cgl.ucsf.edu> wrote:
Thank you Elaine. The problem is that the AlfaFold structures are devoid of side chains. Is there a way to get round this problem?
Have a good day
George
On 9 Jul 2023, at 17:29, Elaine Meng <meng@cgl.ucsf.edu> wrote:
Hi George, The approach that you described is the same that I would try. Hopefully the cysteine will be in the right place. Best, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Department of Pharmaceutical Chemistry University of California, San Francisco
On Jul 8, 2023, at 3:33 AM, George Tzotzos via Chimera-users <chimera-users@cgl.ucsf.edu> wrote:
I’d be grateful for any suggestions regarding the following problem/question.
Problem Placing of the haem-iron centre in mosquito P450 structure(s) obtained by means of AlfaFold. This is required for follow up docking simulations. There no insect P450 structures deposited in PDB. However, there are numerous mammalian P450 crystal structures some of which are homologous to the mosquito structures I’m dealing with. A distinctive feature of these structures is a haem-iron centre tethered to the protein via a cysteine thiolate ligand. Six regions have been designated as substrate recognition sites (SRS 1-6) based on comparative sequence analysis methods. These SRS are conserved and are thought to participate in the formation of the substrate access channel, and form part of the catalytic site surrounding the haem iron center.
My initial approach would be to use Chimera to align the AlfaFold structure against its mammalian homologue PDB structure and assume that the haem-iron centre would be located in the same place.
Is there a better way to achieve the same objective?.
Your help will be greatly appreciated.
Best regards
George
_______________________________________________ Chimera-users mailing list -- chimera-users@cgl.ucsf.edu: To unsubscribe send an email to chimera-users-leave@cgl.ucsf.edu Manage subscription:
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participants (2)
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Elaine Meng -
George Tzotzos