Friday 30 September 2011

Structure problem

From: #HEW KAI LI KELLY#
Date: 13 September 2011 09:55


Hi,

I am facing some problems in solving my structure now, so I am wondering if anyone is able to give me any tips and tricks on this matter.

My protein-DNA complex structure diffracted to 1.5A. There are 4 missing residues, 2 on each terminal. There is no twinning in the data. The angles, the bonds, the rotamers and the Ramachandran plot are okay too. I am using molecular replacement for the phasing and the sequence homology between my protein and my homologous model is 33%. The electron density map for the protein looks very nice and there is also nice density for the DNA. Rfree converged from the initial 39%. However, Rfree refused to go down any further and it's still around 30-31%. Does anyone have any suggestions for me? Thank you in advance!

Warmest Regards,
Kelly Hew




----------
From: Eleanor Dodson


Are you absolutely sure of the spacegroup?

Eleanor

----------
From: Vellieux Frederic


Hi there,

In crystallography there are so many places where you can have problems (and need to solve these problems) that I cannot list them all.

"There is no twinning in the data" - you probably mean "the data does not seem to indicate the presence of twinning but there might be twinning"; what about the space group ? What about your crystal appearing to have one space group for one component (example the protein) but the space group for the other component (e.g. DNA, which could be partially disordered, that happens) being different - and you have processed the data in the apparent space group for the protein ? The crystal could contain the protein:DNA complex plus one of the components needed for the whole thing to pack (and form the crystals); the model might be sufficiently different from "your" structure that all the loops plus a good part of the core is improperly positioned - or you have domain and subdomain "motions" etc etc.

There is one symptom: R-free seems to be stuck. What the reason is for this is unknown. There are cases in the literature where molecular replacement leads to this behaviour and where the crystallographers have to use experimental phasing (and understand what the problem was with molecular replacement afterwards, when the structure is solved).

Fred.
*
*
*
*
*
*


----------
From: Ed Pozharski


And you have built the DNA already, right?


--
Oh, suddenly throwing a giraffe into a volcano to make water is crazy?
                                               Julian, King of Lemurs

----------
From: Kay Diederichs


density for the DNA. Rfree converged from the initial 39%. However,

Hi,

pls check out <http://strucbio.biologie.uni-konstanz.de/ccp4wiki/index.php/Refinement>

To get more specific help, you'll have to tell us much more - number of residues and bases, spacegroup, ... (at least) everything that would end up in "Table 1" of your paper describing the structure, and in the header of the PDB file.

HTH,

Kay
--
Kay Diederichs              .



----------
From: Yuri Pompeu


Just echoing what has been said.
I would make sure you have the right space group.
It may be worthwhile tyring to find a MR solution in different space groups with different compositions.
Another imporatant thing is how complete is your model?
Do you have all the protein and DNA modeled in? How many waters (you should see plenty at 1.5 A)
How good is the difference map?
These are all things that should be checked before panic sets in....

Cheers


No comments:

Post a Comment