Peter from you description seems that big blob is not your ligand. In 3.0
resolution molecules with similar size, including ligands, tend to look
similar in shape as well. I suggest you refine further your structure and
check again later this N-terminal blob of density. It may tern out to be a
bias from your molecular replacement model. If it is still there I will
suggest to rum a MS and compare the MW with the one from your protein
structure. That will give you an indication that probable you have something
attached to N-terminal of your protein.

George 

 

 

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From: CCP4 bulletin board [mailto:[email protected]] On Behalf Of peter
hudson
Sent: Thursday, April 02, 2009 9:55 AM
To: [email protected]
Subject: [ccp4bb] ligand refinemnet

 

Hello all

I have refined and built model a dataset of 3.0A resolution dataset. This
model is assocaied with a ligand. After final refinement and model building
i found  a big blob of  Fo-Fc density of around 4sigma level at the
N-terminal of the fianl model. My protein doesnot carry any tag at the
N-terminal. But, the template i have used for the molecular replacement
carrying a tag at the N-termianl, which can occupy only 1/4th of this
positive density after superpostion. My crystallisation conditions component
cannot occupy such higher level of positive density. Since my protein binds
to a ligand, i looked carefully to the positive density and it seems very
similar to the ligand density but its obscure. Refinement after fitting the
ligand leads to very high B-factor of  the ligan, which vary for various
atoms from 50-90 and simultaneously positive density goes off. I also tried
to change the occupancy of the ligand but as i reduce the occupancy the B
factor comes down at the noraml expected average B factor value but again
Fo-Fc density appears in the map over ligand. If i leave to refine the
occupancy to the programme automatically, this lead to the zero occupancy of
the few atoms in the ligand and avearge B factor remains normal.
suggestions  would be appreciated.

Thanks in advance
Peter 

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