[phenixbb] Overlapping ligand-protein side chain density

Pavel Afonine 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:

refinement {
   refine {
     occupancies {
       constrained_group {
         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 
> phenix.refine"
> http://phenix-online.org/newsletter/
> You can do it in the GUI too.
> Let us know if you more questions or problems!
> Pavel
> 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>>
>>>     wrote:
>>>     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
>>>     too:www.biorxiv.org/content/early/2018/01/24/253419
>>>     <http://www.biorxiv.org/content/early/2018/01/24/253419>
>>>     H
>>>     *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
>>>     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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