Unlike macromolecular crystallography, small molecule crystallography is
infrequently starved for data. So it makes no sense at all to extend
your data to e.g. I/sigI of 1.0 amd Rmeas > 80% unless you want your R1
to be >10% for no good reason or utility, which is what was behind my
suggestion - test to see if the data cutoff is an issue. Also about the
fastest test you can do in SHELXL.
> Yes, ANIS and adding hydrogens (in SHELXL) are good things to do -
with 0.8Å data most small molecule crystallographers would do this as a
first step after fitting all the non-H atoms.
Actually, adding AnisoB's and hydrogens too soon will mess up your
disorder modeling, so blanket statements like that work for well-behaved
structures but not so much for more challenging ones.
e.g. in one of the the four structures I've done this week, one had
significant main-molecule disorder so that comes ahead of adding
hydrogens, and refining unrestrained anisoB (as is the default) for
disordered atoms is asking for trouble. It's not as cookie-cutter as
you represent, and I stick to all my suggestions.
Phil Jeffrey
Princeton
On 6/4/21 4:27 AM, Harry Powell - CCP4BB wrote:
Hi
Yes, ANIS and adding hydrogens (in SHELXL) are good things to do - with 0.8Å
data most small molecule crystallographers would do this as a first step after
fitting all the non-H atoms.
One thing I can’t agree with is to cut the resolution of your data _unless_ you
have a very, very good reason to do so. Normal small molecule refinements will
use data to ~0.8Å and not use a cut-off based on resolution or I/sig(I). A good
dataset will often go to higher resolution and small molecule crystallographers
will be very happy to use these data (unless, as I say, they have a very good
reason not to), and would certainly have to “explain to the referees” why they
didn’t if they ignored a systematic chunk.
Something else that you might not have thought of - have you actually told
SHELXL what the reflection data are - i.e., are they F, F^2, intensity? It’s
perfectly possible to solve a small molecule structure by e.g. telling the
program you’re giving it F^2 but actually giving it F, but refinement would be
somewhat less straightforward. SHELXL normally uses F^2 in refinement,
macromolecular programs still normally use F (AFAIK).
What programs did you use for processing the diffraction data?
Of course, lowering the R factor is not the objective of the exercise - a lower
R-factor is a consequence of having a model that fits the data better.
I would be strongly inclined to ask a small molecule crystallographer (or someone
with a strong background in it) to have a look at your data & model - they
could probably give you a definitive answer by return of e-mail.
Just my two ha’porth
Harry
On 4 Jun 2021, at 03:10, Jon Cooper
<0000488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote:
Agreed, ANIS is the command to try.
Sent from ProtonMail mobile
-------- Original Message --------
On 3 Jun 2021, 20:18, Philip D. Jeffrey < pjeff...@princeton.edu> wrote:
R1 of 17% is bad for small molecule.
0.8 Å is in the eye of the beholder - if you're using macromolecular cutoffs
then these might be too aggressive for small molecule-type refinement stats -
try a more conservative cutoff lie 0.9 and see how that changes R1. However I
suspect it's more to do with how your model is fitting the data.
Have you refined anisotropic Bfactors ?
Have you added hydrogens ?
I would suggest non-CCP4 programs like Olex2 or SHELXLE as the interface for
the refinements - I use the latter and it's somewhat Coot like with useful
features that are particular to small molecule. Also PLATON has some things
(like expand-to-P1 and Squeeze) that, respectively, might be useful to explore
space group issues and disordered solvent. PLATON also has a means to check
for some forms of twinning.
Phil Jeffrey
Princeton
From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of Jacob Summers
<000060a137e4bf3a-dmarc-requ...@jiscmail.ac.uk>
Sent: Thursday, June 3, 2021 2:49 PM
To: CCP4BB@JISCMAIL.AC.UK <CCP4BB@JISCMAIL.AC.UK>
Subject: [ccp4bb] Lowering R factor from small molecule structure
Greetings!
I am currently trying to reduce the R factor of a cyclic small molecule peptoid
in ShelXle. The max resolution of the molecule is 0.8 angstroms. The molecule
itself fits the density very well, but there are a few unexplained densities
around the molecule which do not seem to be anything in the crystallization
conditions. The R1 factor of the refinement is 17.07% but I am unsure how to
lower this value. Any ideas on how to better refine this molecule or fill
densities to lower the R1 factor? I do not have much experience working with
small molecule refinement or with ShelX.
Thanks so much,
Jacob Summers
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