Hi Just my two ha’porth.
I’m currently involved in a project where my collaborators are investigating the interactions between protein pairs (both hetero and homo) - they specifically asked me _not_ to give them any models from ensembles (actually, they said “no NMR structures because they are ensembles") - because (unless they try their “docking” with every member of the ensemble) they have no idea which member of the ensemble they should use for their studies. If you don't actually know how the different parts of a protein are oriented with respect to itself, how can you know how they will be disposed to another protein? Which is not to say you shouldn’t try (or even that I’m right) - what it does indicate is that if you include ensembles (from any source) you are going to make your life harder and also possibly cast doubt on the results. Harry > On 15 Aug 2021, at 14:57, Krieger, James M <krieg...@pitt.edu> wrote: > > It is possible to get an ensemble for an intrinsically disordered segment > from NMR. We did this in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008819/ > > Best wishes > James > >> On Aug 15, 2021, at 14:48, Jon Cooper >> <0000488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote: >> >> Hello, my numpty-level understanding is that being intrinsically disorder >> and giving high-resolution structural data are mutually exclusive. I will >> re-read your e-mails. Hope this helps. Cheers, Jon.C. >> >> >> Sent from ProtonMail mobile >> >> >> >> -------- Original Message -------- >> On 15 Aug 2021, 09:16, Sorin Draga < sor.dr...@gmail.com> wrote: >> >> Hello Ethan, >> >> Thank you for the suggestions. I should have mentioned in my initial post >> that my intention is to first conduct a high throughput virtual screening on >> these proteins, thus I would need high "resolution" of the structures which >> SAXS could not provide, as far as I understand. >> SAXS/SAS might become useful at a later stage, when I have a small number of >> potential inhibitors identified. >> >> Kind regards, >> >> Sorin >> >> On Sat, Aug 14, 2021 at 5:55 PM Ethan A Merritt <merr...@uw.edu> wrote: >> It is possible that you could address some of your questions >> more quickly and much more cheaply by small-angle scattering, >> either light (SAS) or X-ray (SAXS). >> >> I would suggest looking into those avenues first. >> >> If you have well behaved (i.e. non-aggregating) purified proein >> and access to synchrotron beam time (easily requested), >> a series of SAXS experiments could probably be conducted in one day. >> I don't want to oversell SAXS, I'm not really an enthusiast. >> But this case, categorizing the interaction of two poorly ordered proteins >> in solution and in particular the facilitation or disruption of this >> interaction by small molecules, should be well within its scope. >> >> best >> >> Ethan >> >> On Saturday, 14 August 2021 14:12:40 PDT Sorin Draga wrote: >> > Hello everyone, >> > >> > I do realize that this is not a NMR focused group, but I do hope that there >> > are a few spectroscopists lurking around that could possibly answer a few >> > questions (I am more of a modeler/computationalist): >> > >> > The problem: I have two intrinsically disordered proteins that are known to >> > interact (let's call them 1 and 2). I would like to get structural >> > information (a conformational ensemble) for 1 and for the "complex" (1+2). >> > Further down the line (depending on whether this is possible) I would also >> > like to evaluate potential small molecule inhibitors for the said complex. >> > Both 1 and 2 are <200 aminoacids long. >> > >> > The questions: >> > >> > 1. Could the cost of determining the "structure" for 1 and 1+2 be >> > estimated? To be more precise, I am looking for a ball-park figure on how >> > much a NMR measurement would cost in this case. >> > 2. Could anyone recommend a good group/CRO that could provide such a >> > service and not have an astronomical cost? >> > 3. Any other suggestions/thoughts that you think might be worth mentioning >> > (minimum quantity of protein necessary, purity, type of NMR etc) >> > >> > Many thanks for your help and time! >> > >> > Cheers! >> > >> > Sorin >> > >> > ######################################################################## >> > >> > To unsubscribe from the CCP4BB list, click the following link: >> > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=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/ >> > >> >> >> -- >> Ethan A Merritt >> Biomolecular Structure Center, K-428 Health Sciences Bldg >> MS 357742, University of Washington, Seattle 98195-7742 >> >> >> >> To unsubscribe from the CCP4BB list, click the following link: >> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 >> >> >> To unsubscribe from the CCP4BB list, click the following link: >> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 >> > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 > ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=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/
