As Robbie says, in such a case I just blindly refine with local NCS
restraints - this should improve the greater part of the model and thus
provide you with clearer maps. It is quite common for different copies of
the monomer to have differences - after all the crystal environment will be
different - but this should become clearer as refinement progresses. The
programs are pretty good at smudging out errors - B values usually go sky
high, and once you have a better map you can set the occupancies of the
poorly ordered bits to0.00 and see what, if anything comes back.
Eleanor

On Wed, 12 Apr 2023 at 10:27, Robbie Joosten <[email protected]>
wrote:

> The fact that your protomers have different density levels does not mean
> they are structurally different. The prior assumption should be that they
> are the same unless proven otherwise. So I would keep the (local!) NCS
> restraints in the initial stages and only remove them if it becomes
> apparent that this hurts refinement. No need to worry about the density
> averaging out. The models may average out but the density should still have
> enough signal to show any real differences.
>
> HTH,
> Robbie
>
> > -----Original Message-----
> > From: CCP4 bulletin board <[email protected]> On Behalf Of Nitin
> > Kulhar
> > Sent: Wednesday, April 12, 2023 10:02
> > To: [email protected]
> > Subject: [ccp4bb] NCS consideration during refinement vis-a-vis ligand
> > occupancy and flexible loops
> >
> > Hello all
> >
> > I am writing to request opinions from the community regarding the
> following:
> >
> > Situation: An ASU comprising a non-crystallographic homo-octamer of a
> > biological monomer was obtained from MR. Electron density in the initial
> 2Fo-
> > Fc, as well as Fo-Fc maps, seems to vary widely* across the eight
> protomers for
> >
> > *     the supposedly co-crystallized ligand (Kd ~100 micro-molar,
> determined
> > with ITC) and
> > *     1-2 flexible loops (too far from the ligand to interact with it
> directly)
> >
> >
> > Decision: Before commencing to do refinement in such a case, would it be
> > advisable to omit the flexible loops / binding site residues from the NCS
> > reference group to avoid inadvertently averaging out the density of
> structural
> > elements with partial occupancies (ligands and flexible loops)?
> >
> > * varying from non-existent in some protomers to huge unmodeled blobs in
> > others.
> >
> > Please write for any clarifications / further details. I would be highly
> grateful for
> > any help in this regard.
> >
> > Best regards.
> >
> > Nitin Kulhar
> >
> > PhD student
> > c/o Dr Rajakumara Eerappa
> > Macromolecular Structural Biology Group
> > Indian Institute of Technology Hyderabad
> > Kandi, Sangareddy
> > Telangana, India - 502285
> >
> > Disclaimer:- This footer text is to convey that this email is sent by
> one of the
> > users of IITH. So, do not mark it as SPAM.
> >
> >
> > ________________________________
> >
> > To unsubscribe from the CCP4BB list, click the following link:
> > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1
>
>
> ########################################################################
>
> To unsubscribe from the CCP4BB list, click the following link:
> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1
>
> This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a
> mailing list hosted by www.jiscmail.ac.uk, terms & conditions are
> available at https://www.jiscmail.ac.uk/policyandsecurity/
>

########################################################################

To unsubscribe from the CCP4BB list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1

This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list 
hosted by www.jiscmail.ac.uk, terms & conditions are available at 
https://www.jiscmail.ac.uk/policyandsecurity/

Reply via email to