Dear Joel and Herman,
On 15/04/14 04:39, herman.schreu...@sanofi.com wrote:
Dear Joel,
I always tell our chemists not to include piperazine rings etc. in
their compounds because of this conformational mess, but somehow they
do not seem to listen. ;-)
Unfortunately, do did not tell us how and with software you auto
generated your cif file, so I can only give some general remarks:
I would try grade from global phasing to generate your cif file. Grade
uses Mogul, which consults the CSD to find the appropriate
conformational parameters.
Is you nitrogen flat, or has it the wrong chirality? If the chirality
is wrong, you should change all _chem_comp_chir.volume_sign's from
positive/negative to both. However, real-space refinement will usually
not get through the energy barrier to change the chirality, so you
will have to move the atoms manually. In the "Rotate Translate Zone"
mode, you can move individual atoms by pressing <cntrl> and picking
the atom with the left mouse button.
FWIW, for this sort of thing I usually fix atoms before refinement and
ctrl-move fixed atoms during refinement.
If one of the R groups is merely a hydrogen, coot's refinement pathology
detection should jump the hydrogen to the other side of incorrect chiral
centres. You may need to try this in "regularization mode" sometimes.
In my experience, without a formal charge prodrg likes to make
piperazine nitrogens sp2 if connected to at least one aromatic carbon
(as in Joel's case - at least in my reading). This may well be The
Right Thing to do, so the whole boat/chair thing is a bit moot.
If the nitrogen is flat and you auto generate from a pdb file, you
should make sure the nitrogen on the input file has a tetrahedral
conformation. You may force the program to make a tetrahedral nitrogen
by adding a proton (and positive charge) or remove the phenyl and copy
the nitrogen parameters generated to the cif file for the complete
molecule, but better would be to use grade.
Best,
Herman
*Von:*CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] *Im Auftrag
von *Joel Tyndall
*Gesendet:* Dienstag, 15. April 2014 07:03
*An:* CCP4BB@JISCMAIL.AC.UK
*Betreff:* [ccp4bb] appropriate torsion angles
Hi folks,
We are trying to model multiple instances of a small molecule that
contains a piperazine ring. I am looking for the appropriate torsion
angles that are needed for a cif file in order for the piperazine ring
to be able to adopt either a chair or a boat or any combination
between the two (i.e. relaxed torsion restraints but remaining
tetrahedral).
Have you ever seen convincing density for a boat piperazine in PDB data?
(given sp3 hybrization, of course)
Any help would be much appreciated before I launch into writing a new
cif file from scratch.
As a little background, the piperazine contains a phenyl substituent
on the nitrogen which is tetrahedral according to the CSD for small
molecules. This has meant that the auto generated cif files gave the
wrong geometry for the nitrogen in the first place.
Many thanks
