I like both of these points! I would comment/add the following: 1) What are the tools we can use for metals in structural biology? Note, I am biased here.
-Including validation of solute ions like Na/K/Cl etc -Some metric of identity confidence? 2) Micro electron diffraction methods - ability to use on small crystals (which speaks to Tom's point) and a potential bridge between cryo-EM and X-ray diffraction techniques? -What about an XFEL equivalent for electrons with their greater scattering? I looked into this a while back, and there seemed to be some pretty tough things about it, but is there hope? Maybe any purifiable protein could be solved in this way? Would it have to be done by diffraction, or could focusing work somehow? JPK Sarah EJ Bowman, PhD Associate Research Scientist, Hauptman-Woodward Medical Research Institute Director, High-Throughput Crystallization Screening Center https://urldefense.proofpoint.com/v2/url?u=http-3A__www.getacrystal.org&d=DwIF-g&c=LU6cRtx0xgB8s29tIz9Olw&r=eLCg9eJ4Rs_LnxfUWsp7FSxhIEcZYmTSU4Uyq1bRYPI&m=HLRpGMGxTyZSjqW-aeakIElqVXKo3CvO_O36dUmNgKY&s=7uXULBobMzHYWnHc-YO4fFjHH7PbGQXufIRarsr4dQE&e= sbow...@hwi.buffalo.edu ________________________________________ From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of Peat, Tom (Manufacturing, Parkville) <tom.p...@csiro.au> Sent: Monday, July 15, 2019 8:07 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: challenges in structural biology Hello Tim, I'm not sure this question is specific to crystallography- I believe the same can be asked of any experiment in any field? And if one wants to get into true costs- was it worth it to build the Large Hadron Collider to statistically prove that the Higgs boson exists? I'm guessing it was worth it to the folks that got their name on the paper... Cheers, tom -----Original Message----- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Tim Grüne Sent: Tuesday, 16 July 2019 6:09 AM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] challenges in structural biology Dear James, 10) are the biological questions that you can answer with a (crystal) structure sufficiently relevant to justify the resources? Best, Tim Am 15.07.2019 21:44, schrieb Holton, James M: > Hello folks, > > I have the distinct honor of chairing the next Gordon Research > Conference on Diffraction Methods in Structural Biology (July 26-31 > 2020). This meeting will focus on the biggest challenges currently > faced by structural biologists, and I mean actual real-world > challenges. As much as possible, these challenges will take the form > of friendly competitions with defined parameters, data, a scoring > system, and "winners", to be established along with other unpublished > results only at the meeting, as is tradition at GRCs. > > But what are the principle challenges in biological structure > determination today? I of course have my own ideas, but I feel like > I'm forgetting something. Obvious choices are: > 1) getting crystals to diffract better > 2) building models into low-resolution maps (after failing at #1) > 3) telling if a ligand is really there or not > 4) the phase problem (dealing with weak signal, twinning and > pseudotranslation) > 5) what does "resolution" really mean? > 6) why are macromolecular R factors so much higher than small-molecule > ones? > 7) what is the best way to process serial crystallography data? > 8) how should one deal with non-isomorphism in multi-crystal methods? > 9) what is the "structure" of something that won't sit still? > > What am I missing? Is industry facing different problems than > academics? Are there specific challenges facing electron-based > techniques? If so, could the combined strength of all the world's > methods developers solve them? I'm interested in hearing the voice of > this community. On or off-list is fine. > > -James Holton > MAD Scientist > > > ###################################################################### > ## > > To unsubscribe from the CCP4BB list, click the following link: > https://urldefense.proofpoint.com/v2/url?u=https-3A__www.jiscmail.ac.u > k_cgi-2Dbin_webadmin-3FSUBED1-3DCCP4BB-26A-3D1&d=DwIF-g&c=LU6cRtx0xgB8 > s29tIz9Olw&r=eLCg9eJ4Rs_LnxfUWsp7FSxhIEcZYmTSU4Uyq1bRYPI&m=HLRpGMGxTyZ > SjqW-aeakIElqVXKo3CvO_O36dUmNgKY&s=Q23TMeWBhuH2_xEAYk3-wjMz65NwxYH-I3E > fSr0dcAs&e= -- -- 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://urldefense.proofpoint.com/v2/url?u=https-3A__www.jiscmail.ac.uk_cgi-2Dbin_webadmin-3FSUBED1-3DCCP4BB-26A-3D1&d=DwIF-g&c=LU6cRtx0xgB8s29tIz9Olw&r=eLCg9eJ4Rs_LnxfUWsp7FSxhIEcZYmTSU4Uyq1bRYPI&m=HLRpGMGxTyZSjqW-aeakIElqVXKo3CvO_O36dUmNgKY&s=Q23TMeWBhuH2_xEAYk3-wjMz65NwxYH-I3EfSr0dcAs&e= ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://urldefense.proofpoint.com/v2/url?u=https-3A__www.jiscmail.ac.uk_cgi-2Dbin_webadmin-3FSUBED1-3DCCP4BB-26A-3D1&d=DwIF-g&c=LU6cRtx0xgB8s29tIz9Olw&r=eLCg9eJ4Rs_LnxfUWsp7FSxhIEcZYmTSU4Uyq1bRYPI&m=HLRpGMGxTyZSjqW-aeakIElqVXKo3CvO_O36dUmNgKY&s=Q23TMeWBhuH2_xEAYk3-wjMz65NwxYH-I3EfSr0dcAs&e= ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://urldefense.proofpoint.com/v2/url?u=https-3A__www.jiscmail.ac.uk_cgi-2Dbin_webadmin-3FSUBED1-3DCCP4BB-26A-3D1&d=DwIF-g&c=LU6cRtx0xgB8s29tIz9Olw&r=eLCg9eJ4Rs_LnxfUWsp7FSxhIEcZYmTSU4Uyq1bRYPI&m=HLRpGMGxTyZSjqW-aeakIElqVXKo3CvO_O36dUmNgKY&s=Q23TMeWBhuH2_xEAYk3-wjMz65NwxYH-I3EfSr0dcAs&e= ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
