Re: [ccp4bb] Question about small molecule crystallography
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=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 To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
Re: [ccp4bb] Completeness question
Dear all,
On Mon, Jun 01, 2020 at 11:48:41PM +0200, vincent Chaptal wrote:
> since I've been contacted off line several times about this, I'm
> posting here the protocol to combine maps with 2 mtz files of
> original and truncated data.
If this is of wider interest (and since some of our tools for doing
this were mentioned), maybe we can also give a bit of additional
background information and provide some outlook.
> I went through this procedure as I wanted to include the maps, and
> this was the tricky part of the procedure in my hands. This way,
> everyone can look at the same maps when critically assessing a
> structure (especially in the context of redo-ing and severe
> anisotropy).
I think it is a very good idea to also include into the deposition the
maps that were used/seen during model building/refinement. After all,
these were the basis for the interpretation that produced the final
model and the conclusions drawn fom it in a publication. Of course,
one can always re-create similar maps through some external
(re-)refinement approach (be that PDB-REDO or manually using your own
favourite program). Those maps might be similar, better, worse or just
different, perhaps providing added value and additional information -
but it can be difficult to get the exact same maps as seen by the
depositor, due e.g. to different program versions, or to not using the
exact commands and/or parameter settings etc.
Then there is the question of the handling of missing data in 2mFo-DFc
maps (ignoring it, filling it with DFc up to the highest spherical
diffraction limit, or filling it only within the ellipsoidal model of
anisotropy given by STARANISO). BUSTER will create a single mmCIF file
containing all those different map coefficients in separate data
loops. Other programs are most likely to be doing the same. The
important point is that current refinement programs should generate a
single mmCIF file containing all reflection data (and meta-data)
available at the point of refinement - something we are all working
hard at within the PDBx/mmCIF working group. So the task (as described
below) is then to combine this set of reflection data (all nicely
self-contained from model refinement) with the full set of reflection
data (and meta data) from data processing. There are various caveats
and traps one has to consider here (different indexing possibilities,
different cell settings and conventions, enantiomorphs, initially
unassigned screw axes, C2 vs. I2, H3 vs. R3, etc).
Ideally we want an application that takes the two (self-contained)
mmCIF files from data-processing and model refinement, and combines
them in a consistent way, robustly taking care of all of the above
potential issues. Because there often is a large time-gap between
original data-processing and final structure deposition, a lot of
additional checks need to be in place to avoid picking up the wrong
files by accident. This is precisely what we are currently working on
and hope to provide in one of our next releases: a tool working
ideally directly on mmCIF files produced by any data processing
package and any refinement program, that will combine these in a
consistent and validated manner. We hope that will become useful - not
only to users of autoPROC/STARANISO and BUSTER, but also to people who
use multiple different packages in their workflow.
Cheers
Clemens
> In a new directory, put all 3 mtz files (original Intentisties, merged
> staraniso reflections, maps from buster)
>
> /PATH_TO-DIR/BUSTER/Refine45/autoPROC/.
>
> aP_deposition_prep -p combine -r maps.mtz -f staraniso_output.mtz -a
> Original_Intensities.mtz >aP_deposition_prep.log
>
> It creates combine_all.cif
>
> This file has everything but it has a “refln” naming issue.
>
> To fix the “refln” issue:
>
> cat combine_all.cif | sed -e "s/refln.F_sigma /refln.F_meas_sigma /g" -e
> "s%[ ]* #.*from dataset.*%%g" | awk
> '/^#/{if(s){print;next};c++;a[c]=$0;next}/^data/{print;if(s)next;s=1;for(i=1;i<=c;i++){print
> a[i]}next}{print}' > combine_all_refln_fixed.cif
>
> DONE.
>
>
> Best
> Vincent
> ps: again, the credit of this script goes to the globalphasing team who
> kindly helped when I asked them for help with it.
>
>
>
> Le 01/06/2020 à 11:47, Clemens Vonrhein a écrit :
> > Dear all,
> >
> > On Sat, May 30, 2020 at 03:40:53PM +0100, Eleanor Dodson wrote:
> > > My pennysworth. If you find your maps look better after the
> > > anisotroy correction use it, but it may be helpful to those wo want to
> > > mine
> > > your data if you deposit the whole sphere..
> > Agree (which is what e.g. we provide when using STARANISO via autoPROC
> > [1]).
> >
> > And in the same vein: those depositing isotropically truncated data
> > should consider also providing data to a higher diffraction limit to
> > give a potentially more accurate picture (if there is even a slight
> > indication of anisotropy - which there often is).
> >
> > I find it very helpful even looking at an idealised
[ccp4bb] Job posting
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Re: [ccp4bb] [EXTERNAL] Re: [ccp4bb] Question about small molecule crystallography
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 To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
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 To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/ pgpSrJ2FDqtxh.pgp Description: OpenPGP digital signature
Re: [ccp4bb] Question about small molecule crystallography
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 -- This message has been scanned for viruses and dangerous content by MailScanner, and is believed to be clean. To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
Re: [ccp4bb] Question about small molecule crystallography
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 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 >
