Question: Strcuture alignment of multi-chain proteins
gravatar for galleria123
17 months ago by
galleria1230 wrote:

Hello, I have 10,000 models of a 5 chain protein assembly (1SAC.pdb). I need to rank them based on their nativeness (RMSD vs. 1sac.pdb). I have tried multiple tools for this, profitV3.1, maxcluster etc but in all cases I have a problem where models that superimpose very well with the native structure by eye (and which should be native) give very poor rmsd and will therefore be classified as non-native. Conversely, some models which poorly align by eye have a better rmsd with the native structure. Accordingly, I can run the programs but I do not trust their rmsd rankings.

I have tried joining the chains, specifying zones, and iterative fitting but in all cases I have many good models with low scores and many poor models with higher scores. I have been using these tools for some time and never had any problems with monomers and heterodimers. This protein is a homopentamer, I think this is significant in some way.

Any clues out there??

alignment • 526 views
ADD COMMENTlink modified 17 months ago by jrj.healey12k • written 17 months ago by galleria1230
gravatar for jrj.healey
17 months ago by
United Kingdom
jrj.healey12k wrote:

I think there are a few options here.

Firstly, RMSD has been shown to not be a very good metric overall (it can be easily 'tricked'), so you can try your fitting using other programs/metrics like TMalign.

Secondly, try removing 4 of the chains, so that your reference structure only has a single chain. If its a homopentamer it won't matter, and may help your alignments.

That said, I've done a similar thing, whereby all my matching is done using UCSF chimera, and for the most part the models match nicely even to reference structures with 10+ chains (e.g. 3J9Q which contains 2 distinct homohexamers). You're welcome to try this script too if it helps(

Disclaimer: it can be slow, and you'll need to set up pychimera and Chimera but there are instructions at the pychimera github page if needed.

ADD COMMENTlink written 17 months ago by jrj.healey12k
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