[phenixbb] Overlapping ligand-protein side chain density
pafonine at lbl.gov
Thu Mar 1 15:07:11 PST 2018
P.S.: In case you want the occupancies to add up to 1, the constrained
group will be looking like this:
selection = chain A and resseq 123 and resname LIG
selection = chain B and resseq 890 and altloc A
Note two selections in the group, meaning that occupancy of (chain A and
resseq 123 and resname LIG) will be refined and constraied between 0 and
1, occupancy of (chain B and resseq 890 and altloc A) will be refined
and constraied between 0 and 1, and occupancy of (chain A and resseq 123
and resname LIG) plus occupancy of (chain B and resseq 890 and altloc A)
will be 1.
On 3/2/18 06:59, Pavel Afonine wrote:
> Hi Jason,
> Oleg is correct, you can assign the ligand and PHE different non-blanc
> altlocs (say A and B). In this case PHE and ligand will not 'see' each
> other via repulsion term of restraints. Also, their occupancies will
> be refined independently and will be constrained to be within 0 and 1,
> but it will not make sure that they add up to 1. If you want them to
> add up to 1, then make a parameter file with a constrained group as
> described in one of examples here:
> "13 typical occupancy refinement scenarios and available options in
> You can do it in the GUI too.
> Let us know if you more questions or problems!
> On 3/2/18 02:57, Oleg Sobolev wrote:
>> Hi Jason,
>> The ligand and APHE got pushed away from one another and off of
>> their respective densities. Occupancies for both were reduced to
>> 0.5 for the refinement. What am I doing wrong here? Does the
>> ligand need to have an altloc as well? But I don’t see an
>> alternative conformation.
>> Yes, the ligand also needs an altloc, and it should be different from
>> PHE altloc. This way the refinement will know that these atoms don't
>> see each other. You don't have to put two alternative conformations
>> for the ligand, you can have just one with partial occupancy (<1.0)
>> which will mean that the ligand is not always there.
>> Best regards,
>> Oleg Sobolev.
>>> On Feb 28, 2018, at 5:35 PM, van den Bedem, Henry
>>> <vdbedem at slac.stanford.edu <mailto:vdbedem at slac.stanford.edu>>
>>> If the phe is a gatekeeper, shouldn’t the ligand be refined at
>>> partial occupancy; i.e. occupancies not necessarily have to ‘add
>>> up’ as you suggest? Maybe this link is helpful
>>> *From:*<phenixbb-bounces at phenix-online.org
>>> <mailto:phenixbb-bounces at phenix-online.org>> on behalf of "Phan,
>>> Jason" <jason.phan at vanderbilt.edu
>>> <mailto:jason.phan at vanderbilt.edu>>
>>> *Date:*Wednesday, February 28, 2018 at 1:30 PM
>>> *To:*"phenixbb at phenix-online.org
>>> <mailto:phenixbb at phenix-online.org>" <phenixbb at phenix-online.org
>>> <mailto:phenixbb at phenix-online.org>>
>>> *Subject:*[phenixbb] Overlapping ligand-protein side chain density
>>> 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.
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