Complete Protein Structure When Only Alpha Carbons Are Known

Question

[Flow]

For some membrane protein (sequence known) I have found a pdb model that contains only coordinates for alpha carbons (and residue type). Which is the best method for adding/guessing the rest of the atoms pertaining to each residue supposing alpha carbon position is ok?

P.D. If I complete the structure using the sprout server or other, which program/method could I use later for performing energy minimization having already fixed alpha carbons?

P.D.2 Would a good post-approach be to do posterior energy minimization of the resulting structure fixing the alpha carbons? Restrained Molecular Dynamics? Restrained Protein Folding? Which would be the best software for this?

Answer 1

[Naga]

I am not sure about the best method, but here is a tool, MaxSprout, for generating protein backbone and side chain co-ordinates from a C(alpha) trace.

Update: Here is another tool REMO, which constructs protein atomic structures from C-alpha traces by optimizing the backbone hydrogen-bonding networks. You can check out the REMO paper here.

[Keith Callenberg]

This looks like a great tool. One caveat though, is that I think the sidechains are handled a bit simplistically: "To construct full co-ordinates, side-chains are added from a library of frequently occurring rotamers using a simple and fast Monte Carlo procedure with simulated annealing." I think it would be really worthwhile to run the results from MaxSprout through SCWRL (http://dunbrack.fccc.edu/scwrl4/ or online webserver:http://www1.jcsg.org/scripts/prod/scwrl/serve.cgi). It is written by the lab that developed the rotamer libaries that MaxSprout uses (Dunbrack).

[Keith Callenberg]

I would recommend SCWRL itself for this task, but it requires the complete backbone (N,CA,C,O), not just C-alpha atoms.

[Flow]

great, thanks !!

Answer 2

[Jonasr]

Take a look at Nir-Ben Tal's work in:

"Cα-trace model of the transmembrane domain of human copper transporter 1, motion and functional implications" Proc Natl Acad Sci USA.; 2010; DOI: 10.1073/pnas.0914717107; PMID: 20534491

You can get the PDF here: http://ibis.tau.ac.il/wiki/nir_bental/index.php/Publications

Answer 3

[Mndoci]

This might be dated, but I did something like this back in grad school based on work published by and personal communications from Roman Osman's group.

This paper might be the one I am thinking about

http://www.ncbi.nlm.nih.gov/pubmed/8672466

If I recall, I created templates from alpha-Carbon traces, added side chains (in some models I didn't bother with loops, others I did), and did a bunch of refinements to try and come up with a stable structure. Where possible I applied constraints from experimental work being done in our lab.

More information to answer the updated question: IMO with just an Ca-trace to start with you have to use constraints. I liked using harmonic constraints plus any known interactions between residues across segments. Any reasonable MD package should work.

[dimkal]

upvote for mentioning my phd advisor!

[Flow]

which MD package would you recommend for these constraints?

[Mndoci]

I used CHARMM for all my work, but you have a lot more options these days.

Answer 4

[Woa]

Check papers From Harold Scheraga's group. So far I know they have extensively worked on this particular problem

[Flow]

which ones would you recommend?