[ccp4bb] Question about small molecule crystallography

[Jiyuan Ke]

Hi Everyone,

I want to crystallize a small organic molecule. I have very limited
experience in small molecule crystallography. I found that the Crystal
Screen HT from the Hampton research is good for both small molecule and
macromolecule crystallization. Plan to set up a sitting drop screen just
like setting up protein crystallization. I don’t know if this is the proper
way to do it. Is the MRC sitting drop 2-well plate (HR3-083) used for
protein crystallization good for small molecule crystallization? Are there
any special plates used for small molecule crystallization? Is room
temperature ok or not?

For data collection, can I use the beamline for protein crystals to collect
data on small molecule crystals? Larger oscillation angle, shorter
exposure, reduced beam intensity?

For structure determination, is SHELXL the preferred software for solving
small molecule structures?

If anyone has experience in small molecule crystallography, please help.
Thanks!

Best Regards,

-- 

*Jiyuan Ke, Ph.D.*


Research Investigator

H3 Biomedicine Inc.

300 Technology Square, Floor 5

Cambridge, MA 02139

Phone: 617-252-3923

Email: jiyuan...@h3biomedicine.com

Website: www.h3biomedicine.com

-- 
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Re: [ccp4bb] Question about small molecule crystallography

[Artem Evdokimov]

Hi

A small organic molecule is typically crystallized from organic solvents
(or water, if soluble) by means of at least three main techniques:

1. slow evaporation of solvent leading to supersaturation and eventual
crystallization
2. supersaturation at higher temperature followed by gradual drop in
temperature causing crystallization
3. counter-diffusion of an incompatible solvent to drop solubility of the
substance and cause crystallization

Many times, just leaving an NMR tube with a tiny hole in the plastic cap
for a week or so will cause crystals to form.

Schnobviously, some substances will not crystallize easily - some form
oils, amorphous precipitates, etc. and others will form liquid hydrated
forms or just plain decompose. If you have any specific questions please
don't hesitate to contact me in person. I've spent half of my PhD
crystallizing weird small molecules for fun and profit.

As to how to solve structures of small molecules - any synchrotron is a
massive overkill. Just get in touch with a University X-ray lab, many of
which still have functional small molecule instruments. SHELX is the
software of choice - of course! (I still have the blue/white polka dot
SHELX cup, it's one of my more treasured curios).

Artem
- Cosmic Cats approve of this message


On Mon, Jun 1, 2020 at 6:01 PM Jiyuan Ke 
wrote:

> Hi Everyone,
>
> I want to crystallize a small organic molecule. I have very limited
> experience in small molecule crystallography. I found that the Crystal
> Screen HT from the Hampton research is good for both small molecule and
> macromolecule crystallization. Plan to set up a sitting drop screen just
> like setting up protein crystallization. I don’t know if this is the proper
> way to do it. Is the MRC sitting drop 2-well plate (HR3-083) used for
> protein crystallization good for small molecule crystallization? Are there
> any special plates used for small molecule crystallization? Is room
> temperature ok or not?
>
> For data collection, can I use the beamline for protein crystals to
> collect data on small molecule crystals? Larger oscillation angle, shorter
> exposure, reduced beam intensity?
>
> For structure determination, is SHELXL the preferred software for solving
> small molecule structures?
>
> If anyone has experience in small molecule crystallography, please help.
> Thanks!
>
> Best Regards,
>
> --
>
> *Jiyuan Ke, Ph.D.*
>
>
> Research Investigator
>
> H3 Biomedicine Inc.
>
> 300 Technology Square, Floor 5
>
> Cambridge, MA 02139
>
> Phone: 617-252-3923
>
> Email: jiyuan...@h3biomedicine.com
>
> Website: www.h3biomedicine.com
>
>
>
>
>
>
> [This e-mail message may contain privileged, confidential and/or
> proprietary information of H3 Biomedicine. If you believe that it has been
> sent to you in error, please contact the sender immediately and delete the
> message including any attachments, without copying, using, or distributing
> any of the information contained therein. This e-mail message should not be
> interpreted to include a digital or electronic signature that can be used
> to authenticate an agreement, contract or other legal document, nor to
> reflect an intention to be bound to any legally-binding agreement or
> contract.]
>
> --
>
> To unsubscribe from the CCP4BB list, click the following link:
> https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
>



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Re: [ccp4bb] Question about small molecule crystallography

[Peat, Tom (Manufacturing, Parkville)]

Hello Jiyuan,

One small point to note- as Artem says, small molecule crystals are often 
generated out of solvents and these same solvents often melt the standard 
protein crystallisation plates, so be careful what you put into a plastic plate.

As Artem mentioned, synchrotrons are generally overkill for small molecule 
structures (although there are exceptions). In this case, I would like to plug 
for the Australian Synchrotron which has a dedicated small molecule 
crystallographer and a beamline set up for small molecule crystallography (we 
do some protein crystallography there too!). So there is help available for 
those that do want to use synchrotrons for small molecule structures.

cheers, tom

Tom Peat
Proteins Group
Biomedical Program, CSIRO
343 Royal Parade
Parkville, VIC, 3052
+613 9662 7304
+614 57 539 419
tom.p...@csiro.au


From: CCP4 bulletin board  on behalf of Artem Evdokimov 

Sent: Tuesday, June 2, 2020 8:07 AM
To: CCP4BB@JISCMAIL.AC.UK 
Subject: Re: [ccp4bb] Question about small molecule crystallography

Hi

A small organic molecule is typically crystallized from organic solvents (or 
water, if soluble) by means of at least three main techniques:

1. slow evaporation of solvent leading to supersaturation and eventual 
crystallization
2. supersaturation at higher temperature followed by gradual drop in 
temperature causing crystallization
3. counter-diffusion of an incompatible solvent to drop solubility of the 
substance and cause crystallization

Many times, just leaving an NMR tube with a tiny hole in the plastic cap for a 
week or so will cause crystals to form.

Schnobviously, some substances will not crystallize easily - some form oils, 
amorphous precipitates, etc. and others will form liquid hydrated forms or just 
plain decompose. If you have any specific questions please don't hesitate to 
contact me in person. I've spent half of my PhD crystallizing weird small 
molecules for fun and profit.

As to how to solve structures of small molecules - any synchrotron is a massive 
overkill. Just get in touch with a University X-ray lab, many of which still 
have functional small molecule instruments. SHELX is the software of choice - 
of course! (I still have the blue/white polka dot SHELX cup, it's one of my 
more treasured curios).

Artem
- Cosmic Cats approve of this message


On Mon, Jun 1, 2020 at 6:01 PM Jiyuan Ke 
mailto:jiyuan...@h3biomedicine.com>> wrote:
Hi Everyone,

I want to crystallize a small organic molecule. I have very limited experience 
in small molecule crystallography. I found that the Crystal Screen HT from the 
Hampton research is good for both small molecule and macromolecule 
crystallization. Plan to set up a sitting drop screen just like setting up 
protein crystallization. I don’t know if this is the proper way to do it. Is 
the MRC sitting drop 2-well plate (HR3-083) used for protein crystallization 
good for small molecule crystallization? Are there any special plates used for 
small molecule crystallization? Is room temperature ok or not?

For data collection, can I use the beamline for protein crystals to collect 
data on small molecule crystals? Larger oscillation angle, shorter exposure, 
reduced beam intensity?

For structure determination, is SHELXL the preferred software for solving small 
molecule structures?

If anyone has experience in small molecule crystallography, please help.  
Thanks!

Best Regards,

--

Jiyuan Ke, Ph.D.


Research Investigator

H3 Biomedicine Inc.

300 Technology Square, Floor 5

Cambridge, MA 02139

Phone: 617-252-3923

Email: jiyuan...@h3biomedicine.com<mailto:jiyuan...@h3biomedicine.com>

Website: www.h3biomedicine.com<http://www.h3biomedicine.com/>

[https://docs.google.com/uc?export=download&id=0B1VBLPNVMUntenZVa3RFS3JOcVU&revid=0B1VBLPNVMUntbExRa0hyYWpCZGVNeFhZc0JwVit3bzU5c1Z3PQ]





[This e-mail message may contain privileged, confidential and/or proprietary 
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any attachments, without copying, using, or distributing any of the information 
contained therein. This e-mail message should not be interpreted to include a 
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Re: [ccp4bb] Question about small molecule crystallography

[Harry Powell - CCP4BB]

Hi 

Just to echo what has been said before, and expand a little.

(*) 5mm NMR tubes are wonderful for growing small molecule crystals in the way 
Artem describes - partly because they have _extremely_ smooth interior surfaces 
with few nucleation points - so you tend to get fewer, bigger crystals. You 
could also leave the NMR tube sealed, and having run your spectrum at room 
temperature, just “bung it in the ‘fridge or freezer” for a couple of weeks. 
I’ve grown 1st-class crystals by just forgetting the (sealed) nmr tube on my 
bench for a week or so...

(*) PX beamlines are possibly not the best for small molecules because you 
really want to get the high resolution data - say ~0.7Å; a lab-based 
diffractometer in a Chemistry department will do this routinely. If you can 
only grow “tiny" crystals (say << 0.1mm), then you may benefit from a 
synchrotron, but even then a good, modern set-up in a Chem lab would possibly 
still do the job.

(*) I'm being a little picky here, but you don’t use SHELXL to solve structures 
- it’s for refinement. You want one of the structure solution programs like 
SHELXD, SHELXS or SHELXT. If you’re a masochist you could try to get hold of an 
old copy of SHELX-76 and pick your own triplets to solve or try to find the 
heavy atoms “by hand” from thelist of peaks in a Patterson map, and also use 
the same program to refine - but I really, really, wouldn’t recommend it unless 
you don’t have better things to do and don’t mind arguing with referees about 
why you used a program that hasn’t really been developed since Jimmy Carter was 
POTUS!

There are other solutions to solving and refining small molecule structures - 
some I’ve used are Crystals (from the Oxford lab), SIR (in various flavours, 
from Bari), OLEX (from Durham) and Crysalis-Pro (from Rigaku). All work, each 
is slightly different, all are acceptable to all of the major journals.

HTH

Harry

> On 1 Jun 2020, at 23:31, Peat, Tom (Manufacturing, Parkville) 
>  wrote:
> 
> Hello Jiyuan, 
> 
> One small point to note- as Artem says, small molecule crystals are often 
> generated out of solvents and these same solvents often melt the standard 
> protein crystallisation plates, so be careful what you put into a plastic 
> plate. 
> 
> As Artem mentioned, synchrotrons are generally overkill for small molecule 
> structures (although there are exceptions). In this case, I would like to 
> plug for the Australian Synchrotron which has a dedicated small molecule 
> crystallographer and a beamline set up for small molecule crystallography (we 
> do some protein crystallography there too!). So there is help available for 
> those that do want to use synchrotrons for small molecule structures. 
> 
> cheers, tom 
> 
> Tom Peat
> Proteins Group
> Biomedical Program, CSIRO
> 343 Royal Parade
> Parkville, VIC, 3052
> +613 9662 7304
> +614 57 539 419
> tom.p...@csiro.au
> 
> From: CCP4 bulletin board  on behalf of Artem 
> Evdokimov 
> Sent: Tuesday, June 2, 2020 8:07 AM
> To: CCP4BB@JISCMAIL.AC.UK 
> Subject: Re: [ccp4bb] Question about small molecule crystallography
>  
> Hi
> 
> A small organic molecule is typically crystallized from organic solvents (or 
> water, if soluble) by means of at least three main techniques:
> 
> 1. slow evaporation of solvent leading to supersaturation and eventual 
> crystallization
> 2. supersaturation at higher temperature followed by gradual drop in 
> temperature causing crystallization
> 3. counter-diffusion of an incompatible solvent to drop solubility of the 
> substance and cause crystallization
> 
> Many times, just leaving an NMR tube with a tiny hole in the plastic cap for 
> a week or so will cause crystals to form.
> 
> Schnobviously, some substances will not crystallize easily - some form oils, 
> amorphous precipitates, etc. and others will form liquid hydrated forms or 
> just plain decompose. If you have any specific questions please don't 
> hesitate to contact me in person. I've spent half of my PhD crystallizing 
> weird small molecules for fun and profit.
> 
> As to how to solve structures of small molecules - any synchrotron is a 
> massive overkill. Just get in touch with a University X-ray lab, many of 
> which still have functional small molecule instruments. SHELX is the software 
> of choice - of course! (I still have the blue/white polka dot SHELX cup, it's 
> one of my more treasured curios).
> 
> Artem
> - Cosmic Cats approve of this message
> 
> 
> On Mon, Jun 1, 2020 at 6:01 PM Jiyuan Ke  wrote:
> Hi Everyone,
> 
> I want to crystallize a small organic molecule. I have very limited 
> experience in small molecule crystallography. I found that the Crystal Screen 
> HT from the Hampton research is good for both small mole

Re: [ccp4bb] Question about small molecule crystallography

[hoh]

Hi everyone


Pr Tamir gonen (UCLA, los Angeles) have solved (not published) few 
chemical compounds structures with mircoED. And, the more important is 
that crystals were present in the powder (whatever condtions to get it 
(preciptation, evaporation ..). I have myself test with 2 powders coming 
from Chemists, here in Montpellier, and there were bunch of nano 
crystals in both powders, and both diffract at 0.6 A. And, as the 
wavelenght in microED in very short  , Xds or Dials (with some specifics 
parameters) are working well. And ,finally, you need only  around 0.01ug 
of product to put on the grid (without blotting, in dry method) with 
result almost warranty


So, think about microED for small molecules..

FH


François Hoh

Centre de Biochimie Structurale,
UMR 5048 CNRS, UMR 1054 INSERM
29, rue de navacelles
34090 Montpellier Cedex, France.
Phone: +33 467 417 706
Fax:   +33 467 417 913



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Re: [ccp4bb] Question about small molecule crystallography

[Tim Gruene]

Dear Francois,

provided you are not restricted to the trademark term 'microED', but
open minded to include '3D electron crystallography', there are plenty
of published structures of small compounds, both organic and inorganic.
Several of them date back to 2005, and include complex structures
like MOFs, (Xiaodong Zou, Stockholm), twinned structures
(Gemmi/Mugnaioli, Pisa), and really good quality work (Parsons/Zou).

Usually, crystals are not "present in powder", they compose the powder,
in particular if you use products at 99.9% purity from Sigma-Aldrich
'off the shelf' is it was put, and such powders are not
amorphous (if you read bioarxiv) or 'simingly amorphous' (if you read
the peer-reviewed version)...

Scotch is not the same as adhesive tape, and pampers is not the same as
diapers (c.f. also Gerard Bricogne's post on this bb, 29th April 2020).

Best,
Tim



 On Tue, 2 Jun 2020 10:52:45 +0200
hoh  wrote:

> Hi everyone
> 
> 
> Pr Tamir gonen (UCLA, los Angeles) have solved (not published) few 
> chemical compounds structures with mircoED. And, the more important
> is that crystals were present in the powder (whatever condtions to
> get it (preciptation, evaporation ..). I have myself test with 2
> powders coming from Chemists, here in Montpellier, and there were
> bunch of nano crystals in both powders, and both diffract at 0.6 A.
> And, as the wavelenght in microED in very short  , Xds or Dials (with
> some specifics parameters) are working well. And ,finally, you need
> only  around 0.01ug of product to put on the grid (without blotting,
> in dry method) with result almost warranty
> 
> So, think about microED for small molecules..
> 
> FH
> 
> 
> François Hoh
> 
> Centre de Biochimie Structurale,
> UMR 5048 CNRS, UMR 1054 INSERM
> 29, rue de navacelles
> 34090 Montpellier Cedex, France.
> Phone: +33 467 417 706
> Fax:   +33 467 417 913
> 
> 
> 



-- 
--
Tim Gruene
Head of the Centre for X-ray Structure Analysis
Faculty of Chemistry
University of Vienna

Phone: +43-1-4277-70202

GPG Key ID = A46BEE1A



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Description: OpenPGP digital signature

Re: [ccp4bb] Question about small molecule crystallography

[Jessica Bruhn]

Hi Jiyuan,

I don't have much to add on the small molecule crystallization advice, but
I will put in another plug for electron diffraction (microED). You could
first check to see if you already have microcrystal by performing some
X-ray powder diffraction or XRPD (many CROs offer this service). If your
spectra looks good, you can move straight to data collection with electron
diffraction. If you don't already have crystals, I would proceed as
suggested with crystallization trials. If you get big crystals, great! Go
for single crystal X-ray diffraction. If you find that you can only make
microcrystals, I would try to do microED.

Best of luck!


On Mon, Jun 1, 2020 at 3:01 PM Jiyuan Ke 
wrote:

> Hi Everyone,
>
> I want to crystallize a small organic molecule. I have very limited
> experience in small molecule crystallography. I found that the Crystal
> Screen HT from the Hampton research is good for both small molecule and
> macromolecule crystallization. Plan to set up a sitting drop screen just
> like setting up protein crystallization. I don’t know if this is the proper
> way to do it. Is the MRC sitting drop 2-well plate (HR3-083) used for
> protein crystallization good for small molecule crystallization? Are there
> any special plates used for small molecule crystallization? Is room
> temperature ok or not?
>
> For data collection, can I use the beamline for protein crystals to
> collect data on small molecule crystals? Larger oscillation angle, shorter
> exposure, reduced beam intensity?
>
> For structure determination, is SHELXL the preferred software for solving
> small molecule structures?
>
> If anyone has experience in small molecule crystallography, please help.
> Thanks!
>
> Best Regards,
>
> --
>
> *Jiyuan Ke, Ph.D.*
>
>
> Research Investigator
>
> H3 Biomedicine Inc.
>
> 300 Technology Square, Floor 5
>
> Cambridge, MA 02139
>
> Phone: 617-252-3923
>
> Email: jiyuan...@h3biomedicine.com
>
> Website: www.h3biomedicine.com
>
>
>
>
>
>
> [This e-mail message may contain privileged, confidential and/or
> proprietary information of H3 Biomedicine. If you believe that it has been
> sent to you in error, please contact the sender immediately and delete the
> message including any attachments, without copying, using, or distributing
> any of the information contained therein. This e-mail message should not be
> interpreted to include a digital or electronic signature that can be used
> to authenticate an agreement, contract or other legal document, nor to
> reflect an intention to be bound to any legally-binding agreement or
> contract.]
>
> --
>
> To unsubscribe from the CCP4BB list, click the following link:
> https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
>


-- 
Jessica Bruhn, Ph.D
Principal Scientist
NanoImaging Services, Inc.
4940 Carroll Canyon Road, Suite 115
San Diego, CA 92121
Phone #: (888) 675-8261
www.nanoimagingservices.com



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Re: [ccp4bb] Question about small molecule crystallography

[Bernhard Spingler]

Dear Jiyuan,
May I make some advertisement for our tutorial, we published some time ago? Our 
article "Some thoughts about the single crystal growth of small molecules" 
(https://pubs.rsc.org/en/content/articlelanding/2012/ce/c1ce05624g#!divAbstract)
 should exactly answer most of your questions. You will find descriptions about 
different crystallization techniques and which (organic) solvents you can use 
for a start.
If you have further questions, just send me an email.
Best regards
Bernhard


Prof. Dr. Bernhard Spingler
Department of Chemistry
University of Zurich, 34F42
Winterthurerstr. 190
CH 8057 Zurich
Switzerland
http://www.chem.uzh.ch/en/research/spingler.html
sping...@chem.uzh.ch



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Re: [ccp4bb] Question about small molecule crystallography

[Navdeep Sidhu]

Dear Jiyuan,

There was a similar question on the bulletin board some 6 years ago; my
response then (links below) complements some of the other great
suggestions already made in answer to your question:

,
and
.

I believe some 90% of small molecule structures are solved using the
SHELX suite of programs by Prof. Sheldrick, so that should be a great
start. The programs are very easy to use, with great defaults. (There
used to be a joke that to solve this or that problem, all you had to do
is start one of his programs and press enter 5 times.)

As before, I'd highly recommend you read Mueller et al.'s excellent book
with detailed tutorials. It provides the data and walks you through
detailed examples in solving and refining small molecule structures:

Peter Müller, Regine Herbst-Irmer, Anthony Spek, Thomas Schneider and
Michael Sawaya. IUCr/Oxford, 2006
.

I'm sure you'll have much fun doing small molecules in addition to large
molecules. We all did.

All the best,
Navdeep


---
On 01.06.20 23:50, Jiyuan Ke wrote:
> Hi Everyone,
> 
> I want to crystallize a small organic molecule. I have very limited
> experience in small molecule crystallography. I found that the Crystal
> Screen HT from the Hampton research is good for both small molecule and
> macromolecule crystallization. Plan to set up a sitting drop screen just
> like setting up protein crystallization. I don’t know if this is the
> proper way to do it. Is the MRC sitting drop 2-well plate (HR3-083) used
> for protein crystallization good for small molecule crystallization? Are
> there any special plates used for small molecule crystallization? Is
> room temperature ok or not? 
> 
> For data collection, can I use the beamline for protein crystals to
> collect data on small molecule crystals? Larger oscillation angle,
> shorter exposure, reduced beam intensity? 
> 
> For structure determination, is SHELXL the preferred software for
> solving small molecule structures?
> 
> If anyone has experience in small molecule crystallography, please
> help.  Thanks!
> 
> Best Regards,
> 
> -- 
> 
> *Jiyuan Ke, Ph.D.*
> 
> *
> *
> 
> Research Investigator
> 
> H3 Biomedicine Inc.
> 
> 300 Technology Square, Floor 5
> 
> Cambridge, MA 02139
> 
> Phone: 617-252-3923
> 
> Email: jiyuan...@h3biomedicine.com 
> 
> Website: www.h3biomedicine.com 
> 
> 
>  
> 
>  
> 
> 
> [This e-mail message may contain privileged, confidential and/or
> proprietary information of H3 Biomedicine. If you believe that it has
> been sent to you in error, please contact the sender immediately and
> delete the message including any attachments, without copying, using, or
> distributing any of the information contained therein. This e-mail
> message should not be interpreted to include a digital or electronic
> signature that can be used to authenticate an agreement, contract or
> other legal document, nor to reflect an intention to be bound to any
> legally-binding agreement or contract.]
> 
> 
> 
> To unsubscribe from the CCP4BB list, click the following link:
> https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
> 



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Re: [ccp4bb] Question about small molecule crystallography

[Alker, Andre M.]

Dear Jiyuan,

maybe I can add something from the small molecule crystallographer view :-)

Crystallization:
For crystallization of small molecules you normally use solvents and water
or mixtures as mentioned already before. At my lab the most successful way
to crystallise is evaporation. Please use small glass vials (no plastic,
some solvents will solute them too).

You can also use crystallization kits. Here you can use Bernhard Spinglers
kit and or the Hampton kit. The Hampton kit didn't work so well for my
molecules. I also bought Bernhard's kit but had no time to test it so far.
I have to say I'm only using crystallization kits at the moment as last
try. Maybe that changes in the future.

Measurement:
Of course you can use the synchrotron for small molecules at the protein
beamline. I'm using the PXII protein beamline at the SLS (Swiss light
source) for my small molecules if the crystals are too small for my inhouse
system or there is a problem with my inhouse system. To get the resolution
you need for structure solution and a good refinement you have to change
the wavelength to 0.7Å. Collect always at least 360 degrees  in steps of
0.5 degrees or smaller. Use high filters and short exposure times to secure
your crystal against radiation damage. Normally 10 to 20% of the beam and
0.01 to 0.1 sec work fine depending on the crystal size. Do the measurement
at low temperatures as usual for protein crystals. Here are my parameters
for the SLS-PXII beamline equipped with an Eiger detector (wavelength 0.7Å,
biggest aperture, 20% transmission, step 0.1 deg/0.01 sec, 1800 degrees,
100K).

Processing, structure solution and refinement:
I process the eiger data with XDS,
for structure solution I'm using shelxs or shelxd,
for structure refinement shelxl.

But as mentioned before there are a lot of programs doing processing,
structure solution and refinement. I just started to use Olex as well for
solution and refinement. In very earlier times I also used hkl2000 for data
processing but in my opinion XDS is doing a very good job for small
molecule data.

Last but not least I deeply agree with Navdeep to read Mueller et al.'s
excellent book about Crystal Structure Refinement.

Hope this helps a little bit :-)

Best regards,
André






André Alker
Senior Scientist, pCMC Analytics
Roche Pharmaceutical Research and Early Development
Roche Innovation Center Basel
F. Hoffmann-La Roche Ltd
Grenzacherstrasse 124
4058 Basel, Switzerland
Phone: +41-61-6880935
email: andre_m.al...@roche.com

Upcoming absences:
...

Hinweis:
Der Inhalt dieser E-Mail kann vertrauliche Angaben enthalten, die nur für
den (die) namentlich genannten Empfänger bestimmt sind. Falls Sie nicht der
Adressat dieser E-Mail sind, nehmen Sie Verbindung mit dem Absender auf und
löschen Sie diese Mitteilung. Jede unbefugte Verwendung der in dieser
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This message is intended only for the use of the named recipient(s) and may
contain confidential and/or privileged information. If you are not the
intended recipient, please contact the sender and delete this message. Any
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On Wed, Jun 3, 2020 at 7:40 PM Navdeep Sidhu  wrote:

> Dear Jiyuan,
>
> There was a similar question on the bulletin board some 6 years ago; my
> response then (links below) complements some of the other great
> suggestions already made in answer to your question:
>
>  >,
> and
>  >.
>
> I believe some 90% of small molecule structures are solved using the
> SHELX suite of programs by Prof. Sheldrick, so that should be a great
> start. The programs are very easy to use, with great defaults. (There
> used to be a joke that to solve this or that problem, all you had to do
> is start one of his programs and press enter 5 times.)
>
> As before, I'd highly recommend you read Mueller et al.'s excellent book
> with detailed tutorials. It provides the data and walks you through
> detailed examples in solving and refining small molecule structures:
>
> Peter Müller, Regine Herbst-Irmer, Anthony Spek, Thomas Schneider and
> Michael Sawaya. IUCr/Oxford, 2006
> .
>
> I'm sure you'll have much fun doing small molecules in addition to large
> molecules. We all did.
>
> All the best,
> Navdeep
>
>
> ---
> On 01.06.20 23:50, Jiyuan Ke wrote:
> > Hi Everyone,
> >
> > I want to crystallize a small organic molecule. I have very limited
> > experience in small molecule crystallography. I found that the Crystal
> > Screen HT from the Hampton research is good for both small molecule and
> > macromolecule crystallization. Plan to set up a sitting drop screen just
> > like setting up protein crystallization. I don’t know if this is the
> > proper way to do it. Is the MRC sitting drop 2-well

Re: [ccp4bb] Question about small molecule crystallography

[Winter, Graeme (DLSLtd,RAL,LSCI)]

Dear All,

A small word of caution regarding chemical crystallography on an MX-like 
beamline - if you have a bright source, a well diffracting crystal and a pixel 
array detector it is perfectly possible to lose counts in the strongest 
reflections without noticing - certainly without going over the nominal 
detector count limits if your mosaic spread is very small

At Diamond we faced this issue with i19, which is a dedicated chemical 
crystallography beamline on an undulator source, with a Pilatus 2 detector - it 
turns out to be very very easy to exceed the count rate where the detector 
electronics can keep up. This is somewhat less of a problem with Pilatus 3 and 
Eiger 2X detectors.

So: I would strongly suggest really turning down the intensity on the beam, use 
fine slicing and be prepared to check that the data are OK before removing your 
sample. You can solve and refine the structure with e.g. SHELX and get an F^2 
calc vs. I ops plot which would show systematically under measured low angle 
reflections.

We also have a tool in development to bolt on to DIALS called screen19 which 
estimates the true peak photon rate from a “quick screening run” to offer 
insights into data collection options - https://github.com/xia2/screen19 - this 
is not perfect but you could find it useful. Our chemical crystallography users 
certainly find it helpful for planning their experiments.

Best wishes Graeme

On 4 Jun 2020, at 10:51, Alker, Andre M. 
<4599f25026c0-dmarc-requ...@jiscmail.ac.uk>
 wrote:

Dear Jiyuan,

maybe I can add something from the small molecule crystallographer view :-)

Crystallization:
For crystallization of small molecules you normally use solvents and water or 
mixtures as mentioned already before. At my lab the most successful way to 
crystallise is evaporation. Please use small glass vials (no plastic, some 
solvents will solute them too).

You can also use crystallization kits. Here you can use Bernhard Spinglers kit 
and or the Hampton kit. The Hampton kit didn't work so well for my molecules. I 
also bought Bernhard's kit but had no time to test it so far. I have to say I'm 
only using crystallization kits at the moment as last try. Maybe that changes 
in the future.

Measurement:
Of course you can use the synchrotron for small molecules at the protein 
beamline. I'm using the PXII protein beamline at the SLS (Swiss light source) 
for my small molecules if the crystals are too small for my inhouse system or 
there is a problem with my inhouse system. To get the resolution you need for 
structure solution and a good refinement you have to change the wavelength to 
0.7Å. Collect always at least 360 degrees  in steps of 0.5 degrees or smaller. 
Use high filters and short exposure times to secure your crystal against 
radiation damage. Normally 10 to 20% of the beam and 0.01 to 0.1 sec work fine 
depending on the crystal size. Do the measurement at low temperatures as usual 
for protein crystals. Here are my parameters for the SLS-PXII beamline equipped 
with an Eiger detector (wavelength 0.7Å, biggest aperture, 20% transmission, 
step 0.1 deg/0.01 sec, 1800 degrees, 100K).

Processing, structure solution and refinement:
I process the eiger data with XDS,
for structure solution I'm using shelxs or shelxd,
for structure refinement shelxl.

But as mentioned before there are a lot of programs doing processing, structure 
solution and refinement. I just started to use Olex as well for solution and 
refinement. In very earlier times I also used hkl2000 for data processing but 
in my opinion XDS is doing a very good job for small molecule data.

Last but not least I deeply agree with Navdeep to read Mueller et al.'s 
excellent book about Crystal Structure Refinement.

Hope this helps a little bit :-)

Best regards,
André






André Alker
Senior Scientist, pCMC Analytics
Roche Pharmaceutical Research and Early Development
Roche Innovation Center Basel
F. Hoffmann-La Roche Ltd
Grenzacherstrasse 124
4058 Basel, Switzerland
Phone: +41-61-6880935
email: andre_m.al...@roche.com

Upcoming absences:
...

Hinweis:
Der Inhalt dieser E-Mail kann vertrauliche Angaben enthalten, die nur für den 
(die) namentlich genannten Empfänger bestimmt sind. Falls Sie nicht der 
Adressat dieser E-Mail sind, nehmen Sie Verbindung mit dem Absender auf und 
löschen Sie diese Mitteilung. Jede unbefugte Verwendung der in dieser 
Mitteilung enthaltenen Informationen ist untersagt.
This message is intended only for the use of the named recipient(s) and may 
contain confidential and/or privileged information. If you are not the intended 
recipient, please contact the sender and delete this message. Any unauthorized 
use of the information contained in this message is prohibited.


On Wed, Jun 3, 2020 at 7:40 PM Navdeep Sidhu 
mailto:sid...@gmail.com>> wrote:
Dear Jiyuan,

There was a similar question on the bulletin board some 6 years 

Re: [ccp4bb] Question about small molecule crystallography

[00000c2488af9525-dmarc-request]

Re: "it turns out to be very very easy to exceed the count rate where the detector electronics can keep up."Sorry if this is obvious, but I take it you mean "_can't_" keep up?Jon CooperOn 4 Jun 2020 13:06, "Winter, Graeme (DLSLtd,RAL,LSCI)"  wrote:
Dear All,


A small word of caution regarding chemical crystallography on an MX-like beamline - if you have a bright source, a well diffracting crystal and a pixel array detector it is perfectly possible to lose counts in the strongest reflections without
 noticing - certainly without going over the nominal detector count limits if your mosaic spread is very small


At Diamond we faced this issue with i19, which is a dedicated chemical crystallography beamline on an undulator source, with a Pilatus 2 detector - it turns out to be very very easy to exceed the count rate where the detector electronics can keep
 up. This is somewhat less of a problem with Pilatus 3 and Eiger 2X detectors.


So: I would strongly suggest really turning down the intensity on the beam, use fine slicing and be prepared to check that the data are OK before removing your sample. You can solve and refine the structure with e.g. SHELX and get an F^2 calc
 vs. I ops plot which would show systematically under measured low angle reflections. 


We also have a tool in development to bolt on to DIALS called screen19 which estimates the true peak photon rate from a “quick screening run” to offer insights into data collection options - https://github.com/xia2/screen19 -
 this is not perfect but you could find it useful. Our chemical crystallography users certainly find it helpful for planning their experiments. 


Best wishes Graeme


On 4 Jun 2020, at 10:51, Alker, Andre M. <4599f25026c0-dmarc-requ...@jiscmail.ac.uk> wrote:



Dear Jiyuan,


maybe I can add something from the small molecule crystallographer view :-)


Crystallization:
For crystallization of small molecules you normally use solvents and water or mixtures as mentioned already before. At my lab the most successful way to crystallise is evaporation. Please use small glass vials (no plastic, some solvents
 will solute them too). 


You can also use crystallization kits. Here you can use Bernhard Spinglers kit and or the Hampton kit. The Hampton kit didn't work so well for my molecules. I also bought Bernhard's kit but had no time to test it so far. I have to say
 I'm only using crystallization kits at the moment as last try. Maybe that changes in the future.


Measurement: 
Of course you can use the synchrotron for small molecules at the protein beamline. I'm using the PXII protein beamline at the SLS (Swiss light source) for my small molecules if the crystals are too small for my inhouse system or there is a problem
 with my inhouse system. To get the resolution you need for structure solution and a good refinement you have to change the wavelength to 0.7Å. Collect always at least 360 degrees  in steps of 0.5 degrees or smaller. Use high filters and short exposure times
 to secure your crystal against radiation damage. Normally 10 to 20% of the beam and 0.01 to 0.1 sec work fine depending on the crystal size. Do the measurement at low temperatures as usual for protein crystals. Here are my parameters for the SLS-PXII beamline
 equipped with an Eiger detector (wavelength 0.7Å, biggest aperture, 20% transmission, step 0.1 deg/0.01 sec, 1800 degrees, 100K).


Processing, structure solution and refinement:
I process the eiger data with XDS, 
for structure solution I'm using shelxs or shelxd, 
for structure refinement shelxl. 


But as mentioned before there are a lot of programs doing processing, structure solution and refinement. I just started to use Olex as well for solution and refinement. In very earlier times I also used hkl2000 for data processing but
 in my opinion XDS is doing a very good job for small molecule data.


Last but not least I deeply agree with Navdeep to read Mueller et al.'s excellent book about Crystal Structure Refinement. 


Hope this helps a little bit :-)


Best regards,
André



























































André Alker
Senior Scientist, pCMC Analytics
Roche Pharmaceutical Research and Early Development
Roche Innovation Center Basel

F. Hoffmann-La Roche Ltd
Grenzacherstrasse 124
4058 Basel, Switzerland
Phone: +41-61-6880935
email: andre_m.al...@roche.com



Upcoming absences: 
...


Hinweis:
Der Inhalt dieser E-Mail kann vertrauliche Angaben enthalten, die nur für den (die) namentlich genannten Empfänger bestimmt sind. Falls Sie nicht der Adressat dieser E-Mail sind, nehmen Sie Verbindung mit dem Absender auf
 und löschen Sie diese Mitteilung. Jede unbefugte Verwendung der in dieser Mitteilung enthaltenen Informationen ist untersagt.
This message is intended only for the use of the named recipient(s) and may contain confidential and/or privileged information. If you are not the intended recipient, please contact the sender and delete this message. Any unauthorized use of the in

Re: [ccp4bb] Question about small molecule crystallography

[Winter, Graeme (DLSLtd,RAL,LSCI)]

Hi Jon

Ambiguous phrasing, perhaps - the detector has a maximum count rate, as events 
per second, and it is easy to exceed this with a good quality small molecule 
crystal on an undulator beamline thus under record the intensity of strong 
reflections

Best wishes Graeme

On 8 Jun 2020, at 20:55, bogba...@yahoo.co.uk 
wrote:

Re: "it turns out to be very very easy to exceed the count rate where the 
detector electronics can keep up."

Sorry if this is obvious, but I take it you mean "_can't_" keep up?

Jon Cooper

On 4 Jun 2020 13:06, "Winter, Graeme (DLSLtd,RAL,LSCI)" 
mailto:graeme.win...@diamond.ac.uk>> wrote:
Dear All,

A small word of caution regarding chemical crystallography on an MX-like 
beamline - if you have a bright source, a well diffracting crystal and a pixel 
array detector it is perfectly possible to lose counts in the strongest 
reflections without noticing - certainly without going over the nominal 
detector count limits if your mosaic spread is very small

At Diamond we faced this issue with i19, which is a dedicated chemical 
crystallography beamline on an undulator source, with a Pilatus 2 detector - it 
turns out to be very very easy to exceed the count rate where the detector 
electronics can keep up. This is somewhat less of a problem with Pilatus 3 and 
Eiger 2X detectors.

So: I would strongly suggest really turning down the intensity on the beam, use 
fine slicing and be prepared to check that the data are OK before removing your 
sample. You can solve and refine the structure with e.g. SHELX and get an F^2 
calc vs. I ops plot which would show systematically under measured low angle 
reflections.

We also have a tool in development to bolt on to DIALS called screen19 which 
estimates the true peak photon rate from a “quick screening run” to offer 
insights into data collection options - https://github.com/xia2/screen19 - this 
is not perfect but you could find it useful. Our chemical crystallography users 
certainly find it helpful for planning their experiments.

Best wishes Graeme

On 4 Jun 2020, at 10:51, Alker, Andre M. 
<4599f25026c0-dmarc-requ...@jiscmail.ac.uk>
 wrote:

Dear Jiyuan,

maybe I can add something from the small molecule crystallographer view :-)

Crystallization:
For crystallization of small molecules you normally use solvents and water or 
mixtures as mentioned already before. At my lab the most successful way to 
crystallise is evaporation. Please use small glass vials (no plastic, some 
solvents will solute them too).

You can also use crystallization kits. Here you can use Bernhard Spinglers kit 
and or the Hampton kit. The Hampton kit didn't work so well for my molecules. I 
also bought Bernhard's kit but had no time to test it so far. I have to say I'm 
only using crystallization kits at the moment as last try. Maybe that changes 
in the future.

Measurement:
Of course you can use the synchrotron for small molecules at the protein 
beamline. I'm using the PXII protein beamline at the SLS (Swiss light source) 
for my small molecules if the crystals are too small for my inhouse system or 
there is a problem with my inhouse system. To get the resolution you need for 
structure solution and a good refinement you have to change the wavelength to 
0.7Å. Collect always at least 360 degrees  in steps of 0.5 degrees or smaller. 
Use high filters and short exposure times to secure your crystal against 
radiation damage. Normally 10 to 20% of the beam and 0.01 to 0.1 sec work fine 
depending on the crystal size. Do the measurement at low temperatures as usual 
for protein crystals. Here are my parameters for the SLS-PXII beamline equipped 
with an Eiger detector (wavelength 0.7Å, biggest aperture, 20% transmission, 
step 0.1 deg/0.01 sec, 1800 degrees, 100K).

Processing, structure solution and refinement:
I process the eiger data with XDS,
for structure solution I'm using shelxs or shelxd,
for structure refinement shelxl.

But as mentioned before there are a lot of programs doing processing, structure 
solution and refinement. I just started to use Olex as well for solution and 
refinement. In very earlier times I also used hkl2000 for data processing but 
in my opinion XDS is doing a very good job for small molecule data.

Last but not least I deeply agree with Navdeep to read Mueller et al.'s 
excellent book about Crystal Structure Refinement.

Hope this helps a little bit :-)

Best regards,
André






André Alker
Senior Scientist, pCMC Analytics
Roche Pharmaceutical Research and Early Development
Roche Innovation Center Basel
F. Hoffmann-La Roche Ltd
Grenzacherstrasse 124
4058 Basel, Switzerland
Phone: +41-61-6880935
email: andre_m.al...@roche.com

Upcoming absences:
...

Hinweis:
Der Inhalt dieser E-Mail kann vertrauliche Angaben enthalten, die nur für den 
(die) namentlich genannten Empfänger bestimmt sind. Falls Sie nicht der 
Adressat 

Re: [ccp4bb] Question about small molecule crystallography

[James Holton]

It's not all that hard to exceed it with a protein crystal too.

A 50 um wide lysozyme crystal sitting in a 50x50um beam will scatter 
into a single spot up to:


I = 7e-14*flux*(F/mosaic)^2

Where I is in photons/s
flux is incident photons/s
mosaic is in deg
F is the structure factor of the relevant hkl in electrons.

This is the peak photon arrival rate when the hkl is exactly on the 
Ewald sphere.  So, if we have F=130, mosaic=0.02 deg (typical for room 
temp), and flux = 1e12 ph/s we expect a peak count rate of 3e6 ph/s.  If 
that is a 1-pixel spot, then it will exceed the maximum count rate of 
Pilatus2 and Eiger1 detectors (2e6 ph/s).  For lysozyme, 35% of all hkls 
to 2.0A have F > 130.


That said, the "instant retrigger" feature of Pilatus3 and Eiger2 does a 
much better job of correcting for this. Also, spots are usually larger 
than 1 pixel. I often advise room temperature collection with 1 deg 
images on my Pilatus3 because this allows us to run unattenuated. The 
error from the retrigger correction is significantly smaller than the 
error incurred by photons lost in the 1-2 ms gap between images on 
Pilatus.  This second error is all but eliminated by Eiger's much shoter 
read-out period, but only Eiger2 has an instant retrigger feature.


And no, Dectris didn't pay me to say that.

The long and short of it is that whenever you use a counting device your 
intensity data are fundamentally non-linear.  Instant retrigger is just 
one of the various things to try to correct the non-linearity.


How much impact does non-linearity have?  Surprisingly, not that much!  
As long as the non-linearity is uniform across the detector face the 
impact on the more popular data quality metrics is hard to detect if you 
don't know what you're looking for.  It is not hard to test this for 
yourself.  All you need to do is take your favorite dataset's images and 
run the pixels through some non-linear function.  I just tried this with 
a lysozyme dataset using what should be a horrible thing to do: 
new_pixel = 10*sqrt(old_pixel). After doing the same processing and 
refinement protocol both before (normal) and after sqrt-ing the pixel 
values I get:


stat  normal  sqrt-ed
Rwork   17.4  22.0
Rfree   21.7  25.4
CC1/2   99.8  97.6
dmin     1.47  1.55
ISa 15   315
low-res bin:
Rmeas4.7   8.8
I/SIGMA 32.1  32.8
CCano   5936

Ok. ISa is weird, and stats are generally poorer after making the data 
hugely non-linear, but not so poor as to make you suspect something so 
massively wrong with the data.  The anomalous signal is lower, but 
amazingly still there. I suspect this is because anomalous differences 
are relative differences and even wiht a non-linear detector small 
relative differences can still be measured. Food for thought I suppose.


Oh, and read-out noise also doesn't hurt resolution nearly as much as 
you might think.  You can also try this for yourself by adding random 
noise to your pixels, or by simply adding pure background images to your 
data images.  You have to add quite a lot of background before you start 
to notice its impact. This is especially true for poorly-diffracting 
crystals (high WilsonB factor) where the drop in intensity with 
increasing Bragg angle is very steep.  The spots just "shut off" over a 
very narrow range in resolution.  High background can shift the limit 
around in this narrow range, but not by much. Anomalous differences are 
even less sensitive to background than resolution.  This is because the 
"background" for anomalous differences is the spot photons themselves.


You don't believe me, do you?  Try it.  Use merge2cbf to add images 
together. You will find it in your XDS program directory.


-James Holton
MAD Scientist

On 6/8/2020 1:35 PM, Winter, Graeme (DLSLtd,RAL,LSCI) wrote:

Hi Jon

Ambiguous phrasing, perhaps - the detector has a maximum count rate, 
as events per second, and it is easy to exceed this with a good 
quality small molecule crystal on an undulator beamline thus under 
record the intensity of strong reflections


Best wishes Graeme

On 8 Jun 2020, at 20:55, bogba...@yahoo.co.uk 
 wrote:


Re: "it turns out to be very very easy to exceed the count rate where 
the detector electronics can keep up."


Sorry if this is obvious, but I take it you mean "_can't_" keep up?

Jon Cooper

On 4 Jun 2020 13:06, "Winter, Graeme (DLSLtd,RAL,LSCI)" 
mailto:graeme.win...@diamond.ac.uk>> wrote:


Dear All,

A small word of caution regarding chemical crystallography on an
MX-like beamline - if you have a bright source, a well
diffracting crystal and a pixel array detector it is perfectly
possible to lose counts in the strongest reflections without
noticing - certainly without going over the nominal detector
count limits if your mosaic spread is very small

At Diamond we faced this issue with i19, which is a dedicated
chemical crystallography beamline on an undulator source, with a
Pil

Re: [ccp4bb] Question about small molecule crystallography

[Navdeep Sidhu]

Alexander Blake wrote a nice chapter on small-molecule crystallization
in this book, if you run into problems in the crystallization stage:

Alexander Blake. Crystal growth and evaluation (Chapter 3). In Clegg,
William (Ed.) Crystal Structure Analysis: Principles and Practice. 2nd
Edition. IUCr/Oxford, 2009
;
.

With the detector almost but not quite hitting the detector, one can
typically collect all the data one needs on a home Cu source. Overloads
can often be a problem---as has been pointed out out for
synchrotrons---even on a home source. But they can usually be dealt with
easily by modifying exposure, collecting lower- and higher-angle data
separately, leaving some overlap between the two regions (see "Intensity
level", Blake, Ch. 6.7.1, p. 88 in book above) and scaling. In extreme
cases, one may need to lower the generator power.

The nice thing about the slow pace of data collection on a home source
is that one can think while doing the collection, thus catching and
correcting most problems before it's too late. In Ch. 7.6 in the book,
Blake also discusses some other problem cases. (The whole book's a great
read.)

Cheers,
Navdeep



>>> ---
>>> On 01.06.20 23:50, Jiyuan Ke wrote:
>>> > Hi Everyone,
>>> >
>>> > I want to crystallize a small organic molecule. I have
>>> very limited
>>> > experience in small molecule crystallography. I found
>>> that the Crystal
>>> > Screen HT from the Hampton research is good for both
>>> small molecule and
>>> > macromolecule crystallization. Plan to set up a sitting
>>> drop screen just
>>> > like setting up protein crystallization. I don’t know
>>> if this is the
>>> > proper way to do it. Is the MRC sitting drop 2-well
>>> plate (HR3-083) used
>>> > for protein crystallization good for small molecule
>>> crystallization? Are
>>> > there any special plates used for small molecule
>>> crystallization? Is
>>> > room temperature ok or not? 
>>> >
>>> > For data collection, can I use the beamline for protein
>>> crystals to
>>> > collect data on small molecule crystals? Larger
>>> oscillation angle,
>>> > shorter exposure, reduced beam intensity? 
>>> >
>>> > For structure determination, is SHELXL the preferred
>>> software for
>>> > solving small molecule structures?
>>> >
>>> > If anyone has experience in small molecule
>>> crystallography, please
>>> > help.  Thanks!
>>> >
>>> > Best Regards,
>>> >
>>> > --
>>> >
>>> > *Jiyuan Ke, Ph.D.*
>>> >
>>> > *
>>> > *
>>> >
>>> > Research Investigator
>>> >
>>> > H3 Biomedicine Inc.
>>> >
>>> > 300 Technology Square, Floor 5
>>> >
>>> > Cambridge, MA 02139
>>> >
>>> > Phone: 617-252-3923
>>> >
>>> > Email: jiyuan...@h3biomedicine.com
>>> 
>>> >> >
>>> >
>>> > Website: www.h3biomedicine.com
>>> 
>>> 



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Re: [ccp4bb] Question about small molecule crystallography

[Navdeep Sidhu]

Correction: It should read "with the detector almost but not quite
hitting the source."


On 02.07.20 17:13, Navdeep Sidhu wrote:
> Alexander Blake wrote a nice chapter on small-molecule crystallization
> in this book, if you run into problems in the crystallization stage:
> 
> Alexander Blake. Crystal growth and evaluation (Chapter 3). In Clegg,
> William (Ed.) Crystal Structure Analysis: Principles and Practice. 2nd
> Edition. IUCr/Oxford, 2009
> ;
> .
> 
> With the detector almost but not quite hitting the detector, one can
> typically collect all the data one needs on a home Cu source. Overloads
> can often be a problem---as has been pointed out out for
> synchrotrons---even on a home source. But they can usually be dealt with
> easily by modifying exposure, collecting lower- and higher-angle data
> separately, leaving some overlap between the two regions (see "Intensity
> level", Blake, Ch. 6.7.1, p. 88 in book above) and scaling. In extreme
> cases, one may need to lower the generator power.
> 
> The nice thing about the slow pace of data collection on a home source
> is that one can think while doing the collection, thus catching and
> correcting most problems before it's too late. In Ch. 7.6 in the book,
> Blake also discusses some other problem cases. (The whole book's a great
> read.)
> 
> Cheers,
> Navdeep
> 
> 
> 
 ---
 On 01.06.20 23:50, Jiyuan Ke wrote:
 > Hi Everyone,
 >
 > I want to crystallize a small organic molecule. I have
 very limited
 > experience in small molecule crystallography. I found
 that the Crystal
 > Screen HT from the Hampton research is good for both
 small molecule and
 > macromolecule crystallization. Plan to set up a sitting
 drop screen just
 > like setting up protein crystallization. I don’t know
 if this is the
 > proper way to do it. Is the MRC sitting drop 2-well
 plate (HR3-083) used
 > for protein crystallization good for small molecule
 crystallization? Are
 > there any special plates used for small molecule
 crystallization? Is
 > room temperature ok or not? 
 >
 > For data collection, can I use the beamline for protein
 crystals to
 > collect data on small molecule crystals? Larger
 oscillation angle,
 > shorter exposure, reduced beam intensity? 
 >
 > For structure determination, is SHELXL the preferred
 software for
 > solving small molecule structures?
 >
 > If anyone has experience in small molecule
 crystallography, please
 > help.  Thanks!
 >
 > Best Regards,
 >
 > --
 >
 > *Jiyuan Ke, Ph.D.*
 >
 > *
 > *
 >
 > Research Investigator
 >
 > H3 Biomedicine Inc.
 >
 > 300 Technology Square, Floor 5
 >
 > Cambridge, MA 02139
 >
 > Phone: 617-252-3923
 >
 > Email: jiyuan...@h3biomedicine.com
 
 >
 >
 > Website: www.h3biomedicine.com
 
 



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Re: [ccp4bb] [EXTERNAL] Re: [ccp4bb] Question about small molecule crystallography

[Joseph Ferrara]

I would like to point out Rigaku has organized two sets of lectures, via Zoom 
webinar, on the practical aspects of small molecule crystallography. The first 
set of lectures started yesterday while the second set is scheduled to start 
July 6. 

The first lecture, an introduction, is available through our forum, 
www.RigakuXrayForum.com. Today's lecture will cover crystal screening and data 
collection. 

The link to register for the remaining lectures is at 
https://www2.rigaku.com/webinars-past/ and the link to register for the July 
session is at https://www2.rigaku.com/webinars. On those pages you will also 
find other webinars that may or may not be of interest to you. 

Be safe,

Joseph D. Ferrara, Ph.D., NREMR
CSO, Rigaku Americas Corporation
Deputy Director, X-ray Research Laboratory, Rigaku Corporation
Past President, American Crystallographic Association
Secretary-Treasurer, US National Committee for Crystallography
Treasurer, Council of Scientific Society Presidents
Rigaku Americas Corporation
9009 New Trails Drive  •  The Woodlands, TX 77381 USA
T: 281-362-2300  •  M: 281-222-9118  •  S: xrayjoe


-Original Message-
From: CCP4 bulletin board  On Behalf Of Tim Gruene
Sent: Tuesday, June 2, 2020 4:37 AM
To: CCP4BB@JISCMAIL.AC.UK
Subject: [EXTERNAL] Re: [ccp4bb] Question about small molecule crystallography

Dear Francois,

provided you are not restricted to the trademark term 'microED', but open 
minded to include '3D electron crystallography', there are plenty of published 
structures of small compounds, both organic and inorganic.
Several of them date back to 2005, and include complex structures like MOFs, 
(Xiaodong Zou, Stockholm), twinned structures (Gemmi/Mugnaioli, Pisa), and 
really good quality work (Parsons/Zou).

Usually, crystals are not "present in powder", they compose the powder, in 
particular if you use products at 99.9% purity from Sigma-Aldrich 'off the 
shelf' is it was put, and such powders are not amorphous (if you read bioarxiv) 
or 'simingly amorphous' (if you read the peer-reviewed version)...

Scotch is not the same as adhesive tape, and pampers is not the same as diapers 
(c.f. also Gerard Bricogne's post on this bb, 29th April 2020).

Best,
Tim



 On Tue, 2 Jun 2020 10:52:45 +0200
hoh  wrote:

> Hi everyone
> 
> 
> Pr Tamir gonen (UCLA, los Angeles) have solved (not published) few 
> chemical compounds structures with mircoED. And, the more important is 
> that crystals were present in the powder (whatever condtions to get it 
> (preciptation, evaporation ..). I have myself test with 2 powders 
> coming from Chemists, here in Montpellier, and there were bunch of 
> nano crystals in both powders, and both diffract at 0.6 A.
> And, as the wavelenght in microED in very short  , Xds or Dials (with 
> some specifics parameters) are working well. And ,finally, you need 
> only  around 0.01ug of product to put on the grid (without blotting, 
> in dry method) with result almost warranty
> 
> So, think about microED for small molecules..
> 
> FH
> 
> 
> François Hoh
> 
> Centre de Biochimie Structurale,
> UMR 5048 CNRS, UMR 1054 INSERM
> 29, rue de navacelles
> 34090 Montpellier Cedex, France.
> Phone: +33 467 417 706
> Fax:   +33 467 417 913
> 
> 
> 



--
--
Tim Gruene
Head of the Centre for X-ray Structure Analysis Faculty of Chemistry University 
of Vienna

Phone: +43-1-4277-70202

GPG Key ID = A46BEE1A



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