[ccp4bb] CCP4BB vs COVID19
You might think that as a structural biologist you won't be able to do much about COVID-19 anytime soon, but that is not true. Yes, real-world therapeutics and vaccines take time, but we have already seen just how fast we can get started. There are 21 PDBs already and some even have bound ligands. Good job Frank et al. BTW! And my personal thanks to all of you out there who are already hard at work on this. I believe this forum is an ideal place to share information and ideas on the structural biology of SARS-CoV-2 as we move forward. It's a big virus, but there are not that many proteins in it. If all of us independently do the same bioinformatics and literature searches and end up trying exactly the same thing in every lab all over the world, then that would be more than unfortunate. To that end, I am personally interested on ORF8 for reasons I will go into below. Has anyone tried to solve it yet? What happened? Didn't express? Bad diffraction? What? Do tell. Some of us, as you may have heard, are stuck at home, our beamlines and labs dark while we shelter-in-place. That doesn't mean our hands are tied. We are still allowed to think. The fraction of the human race that has a snowball's chance in Hades of figuring out this bug is very very small. Structure may be your main skill set, but you are still a biologist. Do you know how to run a PCR machine? Do you know how to pipette? You might think that anybody can do it, but that is really not the case. Ever trained a new student on sterile technique? How many days did that take? Now remember that your student was no dummy and already studying biology. Everyone reading this will make an excellent volenteer at the very least. I'm not saying this to belittle the average human, only to say that we scientists, moving in the circles we do, often forget that we have uncommon capabilities. For example, I also believe we can be useful in assay development. The void left by the dearth and delay of test results has been filled with fear, and that is a big problem. The tests, as defined, are straightforward, but also extremely regimented like any good laboratory protocol should be. The US CDC's instructions for academic labs are here: https://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html My question is: how can this test be made faster, using more commonplace supplies, in high-throughput mode and still valid? Not just for clinical but for academic use? I think more than a few people on this list could be regarded as experts in making a complex biochemical task faster, more efficient, high-throughput and nonetheless valid. Yes, there are other people who do virus testing for a living, but right now they are all rather busy. Maybe if we put our minds to it we can help? As for why ORF8. I am basing my interest on the bioinformatics done in this article: https://dx.doi.org/10.1093/nsr/nwaa036. Search for "T8517C" and you will find what I'm talking about. The authors found two "types" of SARS-CoV-2. They call them "S" and "L" because the only conserved amino acid change involved is S84L in ORF8. The "S" type is believed to be the ancestor of "L". What is interesting is how tightly linked this mutation is to a silent mutation on the other end of the genome: the "L" type has a faster codon for Ser in ORF1. Such tight coupling (r^2=0.945) means there must be significant selective pressure preventing both of these mutations occurring in the same virus at the same time. That, I believe, is interesting. Espeically since they are so far apart I expect this selective pressure might work in trans: as in a super-infection. That is, the S and L genome types may interfere with each other. The authors fall short of claiming evidence of interference upon super-infection, and indeed they have already been criticised for calling "L" the "aggressive" type. But it is still interesting and points a finger at ORF8. ORF8 has only one homolog in the PDB: 5o32 with 25% identity over a stretch of 60 residues. This homologous region contains the S84L site (Val I544 in 5o32). I had a quick look and appears to be a cavity-filling mutation to me. Not very big, but maybe something could fit in there. To be sure we'd need a structure of ORF8. Good luck to you all, and stay healthy. -James Holton MAD Scientist To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
[ccp4bb] Available SAXS time at Beamline18ID at the APS
The BioCAT beamline 18ID is interested in hosting any SAXS experiments related to Covid-19 research as remote collaborations where samples are sent to us and run by beamline staff. People with suitable projects should contact Srinivas Chakravarthy at schakra...@gmail.com Thanks, Tom Irving Director, Biophysics Collaborative Access Team (BioCAT) To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
[ccp4bb] [ccp4dev] Broken wiki link to dimple from ccp4i
Dear Developers,
from ccp4i classic, the DIMPLE User Guide link (box top right) to
http://ccp4wiki.org/~ccp4wiki/wiki/index.php?title=Automated_difference_map_
generation_with_DIMPLE
returns an error message
"Fatal error: Uncaught TypeError: Argument 1 passed to wfReportException()
must be an instance of Exception, instance of Error given, called in
/home/ccp4wiki/public_html/wiki/includes/Exception.php on line 205 and
defined in /home/ccp4wiki/public_html/wiki/includes/Exception.php:168 Stack
trace: #0 /home/ccp4wiki/public_html/wiki/includes/Exception.php(205):
wfReportException(Object(Error)) #1 [internal function]:
wfExceptionHandler(Object(Error)) #2 {main} thrown in
/home/ccp4wiki/public_html/wiki/includes/Exception.php on line 168"
Can you reproduce that behavior?
Best, BR
--
Bernhard Rupp
b...@hofkristallamt.org
+1 925 209 7429
+43 676 571 0536
--
Many plausible ideas vanish
at the presence of thought
--
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Re: [ccp4bb] Raw diffraction images for SARS-CoV-2 related structures
Dear All, A short note about https://proteindiffraction.org/: If you upload images for an already deposited structure, you dont need to update your PDB entry to provide the DOI. PDB and proteindiffraction.org communicate on a regular basis to link entries to datasets. Ivan With best regards, Ivan Shabalin, Ph.D. Research Scientist, Department of Molecular Physiology and Biological Physics, University of Virginia, 1340 Jefferson Park Avenue, Pinn Hall,Room 4223, Charlottesville, VA 22908 https://www.linkedin.com/in/shabalinig/ https://minorlab.org/person/ivan_s/ On 3/19/20 06:00, John Berrisford wrote: Dear all The wwPDB OneDep system allows depositors to provide DOIs of raw diffraction images during deposition to the PDB and once again encourages depositors to provide a DOI for raw images when they have submitted. Out of the 9665 X-ray entries that were released in 2019 we have DOI's for raw images in 205 of these entries. We would encourage depositors to provide the DOI for their raw images when they are available. Regards John On Mar 19 2020, at 9:48 am, Joel Sussman wrote: 19-Mar-2020 Dear Loes, Peter, Clemens & Gerard, I concur that it is crucial to preserve the original diffraction data and make it available to anyone who would like to use it. As an example, please see the very recent paper by Nachon et al (2020). "A second look at the crystal structures of Drosophila melanogaster acetylcholinesterase in complex with tacrine derivatives provides Insights concerning catalytic intermediates and the design of specific insecticides" Molecules 25 pii: E1198 [https://www.ncbi.nlm.nih.gov/pubmed/32155891]. The study reexamines the original data, with modern software tools, the original data of a paper we published in 2000 (~20 years ago) and revealed features that had not been noticed. Specifically 1) previously unmodeled density in the native active site can be interpreted as stable acetylation of the catalytic serine. 2) Similarly, a strong density in the DmAChE/ZA complex, originally attributed to a sulfate ion, is better interpreted as a small molecule that is covalently bound. The complex is reminiscent of the carboxylate/BChE complexes observed in crystal structures of hBChE [Brazzolotto et al, 2012; Nicolet et al, 2003], and demonstrates the remarkable ability of ChEs to stabilize covalent complexes with carboxylates. Thus, the study demonstrates that updated processing of older diffraction images, and the re-refinement of older diffraction data, can produce valuable information that could not be detected in the original analysis, and strongly supports the preservation of the diffraction images in public data banks. Best regards Joel Prof. Joel L. Sussman. joel.suss...@weizmann.ac.il www.weizmann.ac.il/~joel Dept. of Structural Biology tel: +972 (8) 934 6309 proteopedia.org Weizmann Institute of Science fax: +972 (8) 934 6312 Rehovot 76100 ISRAEL mob: +972 (50) 510 9600 - On 19 Mar 2020, at 11:32, Kroon-Batenburg, L.M.J. (Loes) wrote: Dear Gerard, This is a great idea. Of course I am very much in favour of making available raw diffraction images, and such a virtual workshop could demonstrate the usefulness of reprocessing raw diffraction data and structural refinements. I am not at all afraid that archiving of raw data that are the basis of a scientific paper will have significant environmental effects: this is minor compared to our everyday use of cloud services. And as Graeme mentioned: when archiving raw data make sure to add sufficient and correct meta data. Best wishes, Loes ___ Dr. Loes Kroon-Batenburg Dept. of Crystal and Structural Chemistry Bijvoet Center for Biomolecular Research Utrecht University Padualaan 8, 3584 CH Utrecht The Netherlands E-mail : l.m.j.kroon-batenb...@uu.nl phone : +31-30-2532865 fax : +31-30-2533940 Van: CCP4 bulletin board namens Gerard Bricogne Verzonden: woensdag 18 maart 2020 23:30 Aan: CCP4BB@JISCMAIL.AC.UK Onderwerp: [ccp4bb] Raw diffraction images for SARS-CoV-2 related structures Dear colleagues, Perusal and some initial (re-)refinement of the various SARS-CoV-2 protease structures in the PDB seems to indicate that that there might be potential to improve these if refinements could be repeated after some reprocessing and further analysis of the raw diffraction images, rather than against the deposited merged data. This statement should in no way be construed as a criticism of the remarkable achievements of the research groups concerned, who have been operating under tremendous time pressure, but as an exciting opportunity to push methods to their limits on a uniquely significant class of structures. Another consideration is that the various
