[phenixbb] Overlapping ligand-protein side chain density

Dorothee Liebschner dcliebschner at lbl.gov
Wed Feb 28 15:23:07 PST 2018


Your scenario is covered in the newsletter article "13 typical occupancy
refinement scenarios and available options in phenix.refine".

Scenario 7 probably best reflects your case. If I understand your
configuration correctly, Phe should be modeled as double conformation and
then constrained groups between the ligand and one of the Phe conformations
should be defined.

I hope that helps. Let us know if you need more information.

Best wishes,


On Wed, Feb 28, 2018 at 1:29 PM, Phan, Jason <jason.phan at vanderbilt.edu>

> All,
> A piece of a ligand and the side chain of a “gate-keeper” Phe occupy the
> same space with well-defined features observed for both (resolution is 1.7
> A). It looks about 50:50. How do you refine both ligand and protein side
> chain in this case? A couple of phenixbb suggestions for dealing with
> ligand-ligand overlapping density have been considered. With the first
> suggestion, the two entities still clashed and moved apart off of their
> respective densities. The second suggestion is not applicable in this case
> since the other molecule is not a ligand but part of the protein but it was
> tested anyway. Although there was no bumping, the occupancies don’t add up,
> resulting in a big blob of negative density around the ligand piece.
> ------------------------------
> Only two comments:
>    1. At that resolution, constrained group occupancy refinement should
>    work reasonably well (provided you can model the 2 entities). Then you also
>    do not have clashes between the molecules, because Occ(A)+Occ(B)=1, meaning
>    when one (A) is there, the other one (B) is not. This works with refmac
>    (external keyword file); if you need more sophisticated occupancy
>    re/constraints SHELXL may offer more opportunities.
>    2. There is no necessity for the two NCS copies of the binding site to
>    look exactly the same (non-equivalent). Maybe there is a good reason/story
>    (accessibility, contacts etc) for one site to be occupied differently than
>    the other one.
> Best, BR
> ——————————————
> Modeling two molecules that occupy overlapping binding sites in a
> structure simply involves designating them as alternate conformers, with
> the same chain and residue number, and an occupancy that sums to 1.0. For
> example, if you have an AMP and an ADP that occupy the same binding site,
> you would define them as
> AAMP B 501
> BADP B 501
> and initially set the occupancies for the atoms in each conformer to the
> ratio (50:50, 30:70, etc.) that you observe in the density.
> Refinement in this manner is straightforward in PHENIX.
> Diana
> ----------------------------
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