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 
> <[email protected]> wrote:
> 
> Agreed, ANIS is the command to try. 
> 
> Sent from ProtonMail mobile
> 
> 
> 
> -------- Original Message --------
> On 3 Jun 2021, 20:18, Philip D. Jeffrey < [email protected]> 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 <[email protected]> on behalf of Jacob Summers 
> <[email protected]>
> Sent: Thursday, June 3, 2021 2:49 PM
> To: [email protected] <[email protected]>
> 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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