Re: [ccp4bb] [External] Re: [ccp4bb] Structure prediction - waiting to happen

[Xiao, Chuan]

You raised a very good question: why we are asking this question now? Maybe the 
answer is somewhere on the fact that Alphafold is a “revolution” in the 
prediction field (borrow the term from resolution revolution in cryo-EM).

Anyway, when reading all these discussions, it made me think how I came to US 
to learn how to solve a structure. My Master training is more like 
bioinformatics. My second paper has a component of structural homology modeling 
after sequencing some Rice genes. The paper was rejected by the reviewers 
asking how I could proof my structural modeling (prediction) was correct. At 
that time, I decided to learn how to solve the structure to proof my prediction 
is correct. Now, it is interesting to see now the question is on the other 
side. 😊

River

From: CCP4 bulletin board  On Behalf Of Quyen Hoang
Sent: Sunday, April 2, 2023 10:20 AM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] [External] Re: [ccp4bb] Structure prediction - waiting to 
happen


EXTERNAL EMAIL: This e-mail is from a sender outside of the UTEP system. Do not 
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Thank you for having this conversion.
I have heard this question more than once (why is experimental determination 
needed when there is Alphafold) at grant study sections. Some came from 
structural biologists, so hopefully, the discussion here would help them also.
Computational modeling had existed for decades before Alphafold, and no one 
ever questioned then, as far as I am aware, the need for experimental 
determination of the modeled structures regardless of how accurate the 
predicted models may have been (for example an MD state of a point mutation 
using a high-resolution X-ray model as a starting model), so I am confused as 
to why we are asking this question now. In my view, predicted model, as good as 
it may be, is still a prediction.

Cheers,
Quyen
Quyen Hoang, PhD
Associate Professor
Department of Biochemistry and Molecular Biology
Adjunct Associate Professor of Neurology
Principal Investigator of the Stark Neurosciences Research Institute
Indiana University School of Medicine
635 Barnhill Drive
Medical Sciences Building, room MS0013C
Indianapolis, IN 46202
317-274-4371



On Apr 2, 2023, at 10:52 AM, Eugene Valkov 
mailto:eugene.val...@gmail.com>> wrote:


It depends on the problem under investigation. For example, if you propose to 
perform drug discovery with membrane proteins in a lipid/detergent environment 
or study the structural organization of large ribonucleoprotein assemblies, 
then AlphaFold will be of limited value and you should point this out in the 
rebuttal.


If one of your aims is to study a protein, divide it into pieces, and solve 
structures of domains, then this is justifiably questioned by reviewers in 
light of the information provided by structure prediction. Perhaps in the 
reviewer's opinion, there is no need to use substantial funds and time to solve 
that structure. A more competitive proposal may then re-focus on requesting 
resources for using the structural hypotheses to probe the mechanism with more 
ambitious experimental structural aims or to take a deeper dive into the 
function.


As Darwin said, it is not the strongest or the fastest (or even the most 
intellectual!) that survives.

On Sun, 2 Apr 2023 at 11:28, Srivastava, Dhiraj 
mailto:dhiraj-srivast...@uiowa.edu>> wrote:
That’s the point. All these predictions can not replace experiments and they 
should be used only in the absence of experimental structures, that too with 
caution. A biophysicist and structural biologist understand this but most of 
the non-experts (including the reviewers of the grants from non-structural 
biology study sections) don’t understand this and think that with alphafold, 
there is no need for experimentally determined structures. That’s more damaging 
than helpful.



From: CCP4 bulletin board mailto:CCP4BB@JISCMAIL.AC.UK>> 
on behalf of Eugene Valkov 
mailto:eugene.val...@gmail.com>>
Sent: Sunday, April 2, 2023 10:10 AM
To: CCP4BB@JISCMAIL.AC.UK 
mailto:CCP4BB@JISCMAIL.AC.UK>>
Subject: Re: [ccp4bb] [External] Re: [ccp4bb] Structure prediction - waiting to 
happen


Predicted structures lack the precision and accuracy of 
experimentally-determined structures at high resolution with all the benefits 
of unbiased co-discovery of solvent molecules, ions, ligands, etc., bound to 
molecules of interest.


It is also true that AI-assisted structure prediction can be stunningly 
accurate to the level of correctly identifying interfacing residues between 
interacting proteins and accurately recapitulating the architectures of large, 
multi-domain complexes. AI-assisted structure prediction is immensely 
liberating in lowering the threshold to generate testable hypotheses

Re: [ccp4bb] off-topic: experience BioRad NGC vs Aekta Pure

[Xiao, Chuan]

We have a AKTA start and a AKTA Pure. Don’t like the AKTA start at all. The 
software is buggy (command not performed correctly as it should do) but the 
touch screen is OK. By now I have changed two failed/leaking valves and the UV 
detector for the AKTA start with very light usage. AKTA start uses a 
peristaltic pump that cannot reach high pressure. The gradient is controlled by 
timing between two valves since both buffers are sucked instead of pumped out 
of A and B before mixer. I will not suggest anyone to buy AKTA start. Not a 
very good system. The company will not provide any service for you. You need to 
do all the fixing yourself. If you take out the tubing (as suggested by the 
manual) for the peristaltic pump when not using, the solution will be siphoned 
out to waste line. Poorly designed. Watch those solenoid vales, they are leaky. 
AKTA Pure is a good system but expensive.

Agree with many of you. After changing to Cytiva, the customer service is 
horrible and the whole company become a money sucker. Once I was asking some 
suggestion about configuration changed for AKTA Pure. Two months passed without 
response then asking me how satisfied I was for the service. I gave zero. Then 
they contacted me and give me $3000 quote for remote consulting. I ended up 
just reimaging back the hard drive to recover the setting.

I am still maintaining an very old AKTA FPLC (dark grey machine) using parts 
from eBay. It is still a very good system.

Best,

[cid:image001.jpg@01D73AFE.96DB0800]

From: CCP4 bulletin board  On Behalf Of Kovtun, Oleksiy
Sent: Friday, September 16, 2022 8:48 AM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] off-topic: experience BioRad NGC vs Aekta Pure

Hi Eike,

Instead of AKTA Pure I purchased a combo of AKTA Go (€24k with air sensor) and 
AKta start (€9k with frac collector). It provides two parallel workstations 
with AKTA start handling the dirty job of loading lysates onto affinity 
cartridges and the GO doing clean SEC stages. For multiple proteins isolation, 
this combo beats AKTA Pure flat out for half price. Note that AKTA Start can’t 
be equipped with an air sensor, and sample loading need to be done by time 
control. However, we didn’t find it to be an issue.
Also, AKTA Start needs a separate version of Uncocrn suite for an extra €1k. So 
we skipped that and control the system via the built-in touchscreen.

As for the longevity, we need to see. Six months into active operation went 
smooth—the only malfunction was the Windows update breaking network card 
drivers.

Best,

Oleksiy


Dr Oleksiy Kovtun
Max-Planck Research Group Leader
Molecular Mechanisms of Membrane Trafficking
Max-Planck-Institute for Multidisciplinary Sciences
City-Campus, Hermann-Rein-Str. 3, 37075 Göttingen
Germany
Email: oleksiy.kov...@mpinat.mpg.de
https://www.mpinat.mpg.de/kovtun
Phone:+49-551-3899-410


On 16. Sep 2022, at 09:39, Schulz, Eike-Christian 
mailto:eike.sch...@mpsd.mpg.de>> wrote:

Dear all,

I am considering to purchase a chromatography system for routine protein 
purification. The device is supposed to be used in a multi-user environment, 
hence ease of use, ease of training and ease of maintenance is important. I am 
rather looking for a robust system people like to use than a system that comes 
with many bells and whistles that no one dares to touch.


  *   Is there any particularly _bad_ experience with either system?


  *   Is there any specific advantage of one system over the other?


  *   Does anyone have experience about (long-term) stability / performance of 
the systems?


  *   Do you think the higher price-point of the Aekta systems is justified?


With best regards,

Eike





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[ccp4bb] Call for Registration to virtually attend Dr. Michael Rossmann Symposium on Oct 24-26, 2021

[Xiao, Chuan]

Dear CCP4 X-ray crystallographers,

I am writing this email to invite you to attend Dr. Michael Rossmann Symposium 
that will be held on Oct 24-26, 2021.  Dr. Michael Rossmann was a pioneer in 
protein crystallography and we hope you will be interested to come to the 
symposium in memory of him by listening talks from his friends, colleagues, and 
former trainees.

The symposium will be a hybrid one with both in-person and online. The 
in-person registration has been expired but the virtual attending registration 
is still open till Oct 22nd with a fee of $10. Keynote speakers include Dr. 
Felix Ray, Dr. Michael Diamond, Dr. Joachim Frank, Dr. Polly Roy, and Dr. Hao 
Wu. The full agenda can be found in the URL below:

https://web.cvent.com/event/35b1092e-1536-4fdd-9be0-071dadd3bfca/websitePage:17a44d10-f31a-4522-9701-9e8e2d617a86?locale=en-US&tm=p2kY6DqPITXEWCvuLrfvbWtrD_xow-NH9jEWHA0mREw

The registration URL is copied below for you.

https://web.cvent.com/event/35b1092e-1536-4fdd-9be0-071dadd3bfca/summary?locale=en-US&tm=p2kY6DqPITXEWCvuLrfvbWtrD_xow-NH9jEWHA0mREw

Thank you.

[UTEP]

Chuan (River) Xiao
Professor of Biochemistry
2020 UT System Regents Outstanding Teaching Award Recipient

Department of Chemistry and Biochemistry
The University of Texas at El Paso
500 W. University Ave.
El Paso, TX 79968
Office: 915-747-8657
Fax: 915-747-5996
http://utminers.utep.edu/cxiao/






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