[phenixbb] refinement for ligands with alternative conformation

[Nathaniel Echols]

On Mon, Mar 21, 2011 at 6:35 AM,  <zhengyi at msu.edu> wrote:
> I am working on the refinement of a structure about 2.8A, which the
> substrate ligand has an odd conformation. A blob of negative difference
> density about 4.8 sigma between the one portion of the ligand and the other.
> If I break down the ligand into two parts, the negative density disappears,
> however, one part of the ligands does not fit well. We suspect a mixture of
> conformations.
>
> Any suggestions would be appreciated on how to setup refinement for ligands
> with alternative conformation.

In theory it's just like setting up alternate conformations for
protein residues.  However, it sounds like you have something similar
to a partially hydrolyzed ATP, where conformation "A" is ATP, and
conformation "B" is ADP (perhaps in combination with phosphate).
There is nothing in phenix.refine that prevents you from doing this -
unfortunately, it probably requires editing the PDB file manually to
create the alternate conformations and rename the altloc (the column
to the left of the residue name).  For the other half of the
hydrolyzed ligand, if you decide to model this explicitly, I'd
recommend using the insertion code (the column to the right of the
residue number), and leaving the residue number the same.  Thus for
ATP+ADP+Pi, you would end up with:

ATP = conformer A, residue 1
ADP = conformer B, residue 1
Pi = conformer B, residue 1P

Messy, but it should work.

-Nat