Complete Protein Structure When Only Alpha Carbons Are Known
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10.7 years ago
Flow ★ 1.5k

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?

protein prediction model • 5.5k views
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10.7 years ago
Naga ▴ 450

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.

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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).

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

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great, thanks !!

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10.7 years ago
Jonasr ▴ 120

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

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10.7 years ago
Mndoci ★ 1.2k

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.

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upvote for mentioning my phd advisor!

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which MD package would you recommend for these constraints?

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

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10.7 years ago
Woa ★ 2.9k

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

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which ones would you recommend?

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