Hi Mohit,
I was able to get crystals of C111S-PLpro using microbatch under oil method
in crystal screen of hampton research. Protein concentration was around 10
mg/ml. Crystals diffracted to 2.5 A at NSLS-II.

*Dr. Amit Gaur, *
*Department of Biomedical Science,*
*College of Medicine,*
*Florida State University,*
*1115 W Call St, Tallahassee, FL,32304*





On Mon, Jun 30, 2025 at 3:30 PM Edward Snell <
[email protected]> wrote:

> Hi Mohit,
>
>
>
> I would agree with the temperature and seeding comments by Emmanuel.
> Although not proven for diffraction characteristics, volume ratio and
> temperature can be effective optimizing strategies – see Luft et al, 2007  (
> https://hwi.buffalo.edu/wp-content/uploads/2016/12/dvrt.pdf).
>
>
>
> I noticed in looking at a number of models in the PDB that dimethyl
> sulfoxide (DMSO) seems to be significant in the high-resolution models and
> does seem to form key contacts in packing diagrams. Although it’s probably
> there to solubilize some of the ligands tested, it does seem to be ordered
> in the electron density, bridges chains and probably stabilizes them, and
> could be a useful component to add to your current conditions.
>
>
>
> It’s not clear from your comments if you had more than one initial
> crystallization condition that you optimized, but I’d also recommend
> optimizing ‘crappy’ crystals that appear in initial screens if they are
> from chemically distinct conditions. A little optimization can go a long
> way in going from visually poor to diffraction good crystals.
>
>
>
> I think you are heading in the right direction, and the crystals you do
> have are beautiful. I presume you have tried a microfocus beamline, but if
> not, that is also a good approach.
>
>
>
> Best of luck,
>
>
>
> Eddie
>
>
>
> *Edward Snell Ph.D.*
>
> Professor, Materials Design and Innovation | University at Buffalo, SUNY
>
> Director | NSF BioXFEL Science and Technology Center
>
> Fellow of the American Crystallographic Society – The Structural Science
> Society
>
> p: +1 716 898 8631 | f: +1 716 898 8660
> e: esnell@ buffalo.edu <[email protected]>
>
> The University at Buffalo Hauptman-Woodward Institute
> 700 Ellicott Street
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>  |
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>
> Website: https://snelllab.website/
>
>
>
> [image: hwi-logo-primary-horizontal]
>
>
>
>
>
>
>
> *From:* CCP4 bulletin board <[email protected]> *On Behalf Of *Mohit
> Bhardwaj
> *Sent:* Monday, June 30, 2025 3:18 AM
> *To:* [email protected]
> *Subject:* [ccp4bb] Crystallization of SARS-CoV-2 3CLpro and Mutants –
> Seeking Advice on Crystal Optimization
>
>
>
> Dear members, I am currently working on the crystallization of the main
> protease (3CLpro) of SARS-CoV-2, focusing on both the wild-type and several
> point mutants. Initial crystallization trials were c
>
> Warning! This message was sent from outside your organization and we were
> unable to verify the sender.
>
> sophospsmartbannerend
>
> Dear members,
>
> I am currently working on the crystallization of the main protease
> (3CLpro) of SARS-CoV-2, focusing on both the wild-type and several point
> mutants.
>
> Initial crystallization trials were conducted using commercial screens,
> including PACT, JCSG+, and INDEX. These trials yielded crystals of various
> morphologies—predominantly needles, thin sheets, and flower-like clusters.
> To improve crystal quality, I subsequently performed optimization using the
> hanging-drop vapor diffusion method by systematically varying PEG
> concentration, salt types/concentrations, and pH conditions. Despite these
> efforts, the crystals have not shown significant improvement in morphology
> or diffraction quality.
>
> I have also attempted microseeding and macroseeding approaches during
> optimization, but the results remain largely the same. I would greatly
> appreciate any suggestions or experiences from the community regarding
> strategies that could help improve crystal quality in such systems,
> particularly with challenging morphologies like needle or sheet-like forms.
>
> Thank you in advance for your insights.
>
> Mohit Bhardwaj
>
> PhD Scholar
>
> Kusuma School of Biological Sciences
>
> IIT Delhi, Hauz Khas
>
> New Delhi- 110016
>
> Mobile No. : +91-8895172936, 8700227218
>
>
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