[Chimera-users] How to model a 4Fe4S cluster on conserved Cys residues

Elaine Meng meng at cgl.ucsf.edu
Tue Mar 8 13:56:42 PST 2011

On Mar 8, 2011, at 1:03 PM, Ingmar Buerstel wrote:
> Dear Elaine,
> thanx a lot for your quick answer. In fact I have already a modelled structure (made with swiss model) of the protein. 
> I was looking for a possiblitiy to fit a 4Fe4S-cluster in the position of the original cluster. The cysteines are conserved, thus, I just need to copy/paste the 4Fe4S-cluster into my structure. I would be glad, if you could help me concerning this problem. 

Dear Ingmar,
You could superimpose your model and the related structure that does contain this cluster (residue SF4) and then merge the SF4 residue into your model.  However, the result may be rough, depending on how well the structures match in 3D.  It might be better to start over and use Modeller as described in my previous message, because it can make a model that already includes the cluster.

However, if you want to try the superimposing approach, here are more details.

(a) In Chimera, open your model and then open the known related structure that contains the cluster.

(b) Superimpose the two structures, for example with the Matchmaker tool.  Here is some discussion of different ways to superimpose structures in Chimera.  You will want to make sure that the structures match well at the four cysteines.

(c) Delete everything in the known structure except for the part you want to paste into your homology model, and then combine the two models into one.  For example, if your model is open as #0 in Chimera and the known structure is open as #1, you could use commands

delete #1 & ~:sf4

combine #0,1

The delete command gets rid of all atoms in #1 except the SF4 residue.  The combine command creates a new model, #2, by merging the SF4 residue in #1 with the homology model in #0.

 You can save the new model #2 to a file (for example, with File... Save PDB).

However, you would hope that the cysteine sidechains in your model are pointing in the correct orientations to bind the cluster.  If not, you might have to paste in those residues from the known structure too, and delete them from your homology model, before merging.  Then you might have to manually text-edit the PDB to add bonds between the merged cysteines and the rest of the homology model.  Again, it might be better just to start over and use a modelling method that can include the cluster in the first place.

I hope this helps,
Elaine C. Meng, Ph.D. 
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco

> > Subject: Re: [Chimera-users] How to model a 4Fe4S cluster on conserved Cys residues
> > From: meng at cgl.ucsf.edu
> > Date: Mon, 7 Mar 2011 09:38:45 -0800
> > CC: chimera-users at cgl.ucsf.edu
> > To: ingmar_b at hotmail.com
> > 
> > Dear Ingmar,
> > It sounds like you want to model your whole protein including the 4Fe4S cluster, am I right? Or is there a structure of your protein but that does not include the cluster?
> > 
> > I would not recommend modeling this "from scratch" (building one atom by one atom) in Chimera but instead, homology-modeling your protein and cluster from the structure of a related protein that contains the cluster. Of course, this all depends on the existence of a known structure for a related protein. 
> > 
> > Chimera includes an interface to the Modeller program for homology-modeling. To use it, you would have to first go to the Modeller website 
> > <http://www.salilab.org/modeller/registration.html>
> > and register to get a license key (free for academic use). In Chimera, you could choose "Tools... Sequence... Blast Protein," paste in the sequence of your protein, and then blast it against the PDB to see if there are any structures related to your protein. If there is a hit that seems good enough to you, you could use the Blast results dialog to open the structure and also the alignment of the two sequences. 
> > <http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/blast.html>
> > Then, in the sequence alignment window, choose "Structure... Modeller Tools" to show the interface to Modeller. Use "Advanced Option" to "Include non-water HETATM residues from template" so that the FeS cluster will be included in the model.
> > <http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/modeller.html>
> > 
> > Or, you could simply see if there is already a model of your protein available in ModBase by using "File... Fetch by ID" in the Chimera menu. However, those models probably wouldn't contain the FeS cluster.
> > <http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/fetch.html>
> > <http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/modbase.html>
> > 
> > Some related references I just saw but didn't read in detail:
> > 
> > Fee, J. A.; Castagnetto, J.M.; Case, David A.; Noodleman, L.; Stout, C.D.; Torres, R.A.; "The circumsphere as a tool to assess distortion in [4Fe-4S] atom clusters". J. Biol. Inorg. Chem. 2003, 8: 519-526. 
> > <http://dx.doi.org/10.1007/s00775-003-0445-8>
> > 
> > Atomic resolution structures of oxidized [4Fe-4S] ferredoxin from Bacillus thermoproteolyticus in two crystal forms: systematic distortion of [4Fe-4S] cluster in the protein. 
> > (2002) J.Mol.Biol. 315: 1155-1166
> > <http://dx.doi.org/10.1006/jmbi.2001.5292>
> > (goes with PDB entries 1iqz, 1ir0 ... I see that the residue name of the cluster is SF4, so you could also use the searching tools at the PDB website to find structures that have this cluster)
> > 
> > I hope this helps,
> > Elaine
> > On Mar 6, 2011, at 6:44 AM, Ingmar Buerstel wrote:
> > > Dear users,
> > > i hope anybody out there can help me. I would like to model a 4Fe4S cluster in between a set of four highly conserved Cys residues. From compoarative analysis with crystal strucutre I know there belongs a 4Fe4S but for my respective protein no such crystal exists, so I would like to model my 4Fe4S cluster by my self. I am not very familiar with Chimera, yet, but the "Build structure" function did not work quite well for me. 
> > > 
> > > So would kindly ask those who have experince with this kind of models to give me some hinds to model such a FeS-cluster 
> > > Thanx in advance, 
> > > Ingmar 
> > 

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