de novo octahedral assembly of AlphaFold-generated ferritin monomers
Hi folks! I would like to use "Sym # O" to model how a novel marine ferritin might assemble into an octahedral nanocage. Like ferritin, this marine ferritin is thermostable and has a size consistent with a 24-mer, but the AA sequence is too divergent to use 'matchmaker'. I've noticed that if I create a fold model of human ferritin (1FHA) with AlphaFold and import it into ChimeraX, the 'sym # O' command generates a 24-mer hairball rather than an octahedrally-coordinated sphere. If I 'fetch' the same 1FHA protein directly from PDB, the spherical structure is correctly assembled. What additional commands might be needed to help ChimeraX correctly assemble an AlphaFold-generated 1FHA monomer into the canonical ferritin cage? Chimera used to have a 'group 432' command, but I see this is not currently supported. Thanks in advance! Knowing how to correctly assemble something known like human ferritin will greatly help in assembling something unknown like a marine ferritin. Best Regards, Jeff McQuaid, Scripps Institution of Oceanography
Hi Jeff! The octahedral symmetry is applied around a center. So probably the two cases have different centers and the default center is correct (or not obviously wrong) for one but incorrect for the other. The "sym" command has "center" option for specifying the center coordinates, if you know what they are. Perhaps figuring that out would be the hard part. See: <https://rbvi.ucsf.edu/chimerax/docs/user/commands/sym.html#symmetry> I guess another possibility is to superimpose the model onto 1fha (such as with the Matchmaker tool or command) in hopes that they superimpose well enough for the same center to work, but I don't know how successful that would be. I hope this helps, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Resource for Biocomputing, Visualization, and Informatics Department of Pharmaceutical Chemistry University of California, San Francisco
On Oct 3, 2025, at 12:49 PM, jmcquaid--- via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:
Hi folks!
I would like to use "Sym # O" to model how a novel marine ferritin might assemble into an octahedral nanocage. Like ferritin, this marine ferritin is thermostable and has a size consistent with a 24-mer, but the AA sequence is too divergent to use 'matchmaker'.
I've noticed that if I create a fold model of human ferritin (1FHA) with AlphaFold and import it into ChimeraX, the 'sym # O' command generates a 24-mer hairball rather than an octahedrally-coordinated sphere. If I 'fetch' the same 1FHA protein directly from PDB, the spherical structure is correctly assembled. What additional commands might be needed to help ChimeraX correctly assemble an AlphaFold-generated 1FHA monomer into the canonical ferritin cage? Chimera used to have a 'group 432' command, but I see this is not currently supported.
Thanks in advance! Knowing how to correctly assemble something known like human ferritin will greatly help in assembling something unknown like a marine ferritin.
Best Regards, Jeff McQuaid, Scripps Institution of Oceanography _______________________________________________ ChimeraX-users mailing list -- chimerax-users@cgl.ucsf.edu To unsubscribe send an email to chimerax-users-leave@cgl.ucsf.edu Archives: https://mail.cgl.ucsf.edu/mailman/archives/list/chimerax-users@cgl.ucsf.edu/
Sorry, I forgot you mentioned that matchmaker doesn't work (sequences too dissimilar) -- in that case, you could try fitting the backbone atoms of specified residues in the two structures with "match" instead. Since "match" doesn't figure out the alignment for you, you'd have to explicitly give the residue ranges, and since the residue types are different, use only the backbone atoms or some subset of the backbone atoms such as alpha-carbons. Example: match #2:10-88@n,ca,c,o #1:5-83@n,ca,c,o Elaine
On Oct 3, 2025, at 1:54 PM, Elaine Meng via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:
I guess another possibility is to superimpose the model onto 1fha (such as with the Matchmaker tool or command) in hopes that they superimpose well enough for the same center to work, but I don't know how successful that would be.
Semi related - a trick we have used for alignment in cases where the fold is conserved but doesn’t align well with matchmaker is to use molmap to make a map from the target model (perhaps at 12 A to start), then use fitmap to fit the search model to that. Molmap at higher resolution can then be used for more precise alignment. This often works where matchmaker fails. Cheers Oli
On Oct 3, 2025, at 5:06 PM, Elaine Meng via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:
Sorry, I forgot you mentioned that matchmaker doesn't work (sequences too dissimilar) -- in that case, you could try fitting the backbone atoms of specified residues in the two structures with "match" instead. Since "match" doesn't figure out the alignment for you, you'd have to explicitly give the residue ranges, and since the residue types are different, use only the backbone atoms or some subset of the backbone atoms such as alpha-carbons. Example:
match #2:10-88@n,ca,c,o #1:5-83@n,ca,c,o
Elaine
On Oct 3, 2025, at 1:54 PM, Elaine Meng via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:
I guess another possibility is to superimpose the model onto 1fha (such as with the Matchmaker tool or command) in hopes that they superimpose well enough for the same center to work, but I don't know how successful that would be.
_______________________________________________ ChimeraX-users mailing list -- chimerax-users@cgl.ucsf.edu To unsubscribe send an email to chimerax-users-leave@cgl.ucsf.edu Archives: https://mail.cgl.ucsf.edu/mailman/archives/list/chimerax-users@cgl.ucsf.edu/
One more point is that matchmaker was intended even for fairly low sequence similarity. You can downweight the amino acid type part of the score relative to secondary structure, or even omit it entirely (secondary structure score weighting 1.0 instead of 0.3), and/or use a longer-evolutionary-distance residue type matrix. Just another thing to try if you have only tried matchmaker with the default parameters. Whether this works depends on how good a signal there is in alignment of secondary structure elements. Elaine
On Oct 3, 2025, at 2:27 PM, Oliver Clarke <olibclarke@gmail.com> wrote:
Semi related - a trick we have used for alignment in cases where the fold is conserved but doesn’t align well with matchmaker is to use molmap to make a map from the target model (perhaps at 12 A to start), then use fitmap to fit the search model to that. Molmap at higher resolution can then be used for more precise alignment. This often works where matchmaker fails.
Cheers Oli
On Oct 3, 2025, at 5:06 PM, Elaine Meng via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:
Sorry, I forgot you mentioned that matchmaker doesn't work (sequences too dissimilar) -- in that case, you could try fitting the backbone atoms of specified residues in the two structures with "match" instead. Since "match" doesn't figure out the alignment for you, you'd have to explicitly give the residue ranges, and since the residue types are different, use only the backbone atoms or some subset of the backbone atoms such as alpha-carbons. Example:
match #2:10-88@n,ca,c,o #1:5-83@n,ca,c,o
Elaine
On Oct 3, 2025, at 1:54 PM, Elaine Meng via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:
I guess another possibility is to superimpose the model onto 1fha (such as with the Matchmaker tool or command) in hopes that they superimpose well enough for the same center to work, but I don't know how successful that would be.
_______________________________________________ ChimeraX-users mailing list -- chimerax-users@cgl.ucsf.edu To unsubscribe send an email to chimerax-users-leave@cgl.ucsf.edu Archives: https://mail.cgl.ucsf.edu/mailman/archives/list/chimerax-users@cgl.ucsf.edu/
participants (3)
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Elaine Meng -
jmcquaid＠ucsd.edu -
Oliver Clarke