[ccp4bb] Call for targets for the 2024 CASP modeling experiment

[Andriy Kryshtafovych]

CASP (Critical Assessment of Structure Prediction) experiments are held 
every two years. Recent rounds have seen dramatic increases in modeling 
accuracy, resulting from the introduction of deep learning methods: In 
2018, for the first time, the folds of most proteins were correctly 
computed [1]; in 2020, the accuracy of many computed protein structures 
rivaled that of the corresponding experimental ones [2]; in 2022, there 
was an enormous increase in the accuracy of protein complexes [3].


We have seen the beginning of what deep learning methods may achieve in 
structural biology. In addition to further increases in the accuracy of 
protein complexes, methods are being developed for RNA structures, 
organic ligand-protein complexes, and for moving beyond single 
macromolecular structures to compute conformational ensembles. Accurate 
computational methods together with experimental data also offer the 
prospect of probing previously inaccessible biological systems. CASP has 
expanded its scope to provide critical assessment in all these areas.


CASP is only possible with the generous participation of the 
experimental structural biology community in providing suitable targets: 
A total of over 1100 targets have been obtained over the previous CASP 
rounds. We are now requesting targets for the 2024 CASP16 experiment. We 
need challenge targets in the following areas:


Single protein structures: The 2020 and 2022 CASPs showed that, so far, 
Alphafold2 and methods built around it are by far the most accurate [4]. 
But there are limitations, particularly for some proteins where only a 
shallow sequence alignment is available and for very large proteins 
(more than 1000 amino acids). The best results also require substantial 
amounts of computing resources, well beyond that of the AlphaFold2 
default settings. Many new methods are continuing to appear and these 
may remove some of the remaining difficulties. All types of protein 
targets are needed, but especially those with shallow sequence 
alignments, without structural templates, and large proteins.


Protein complexes: In the 2022 CASP15, advanced deep learning methods 
were applied to protein complexes for the first time [5]. The result was 
a huge improvement in accuracy compared with classical docking 
approaches. But overall, the results are still not at the level achieved 
for single proteins. So, in CASP16 we need all sorts of targets in this 
area so as to determine progress since then. We particularly need 
complexes where there is no evolutionary information across the 
protein-protein interfaces, for example, antibody-antigen complexes. 
(This CASP category is conducted in close collaboration with our 
colleagues at CAPRI - Critical Assessment of protein interactions [6]).


Nucleic acid structures and complexes: In recognition of the major role 
nucleic acid structures and complexes play in biology, CASP now includes 
this class of target. A number of papers claiming successful RNA 
structure computation using deep learning methods have been published, 
but those participating in the 2022 CASP RNA category performed less 
well than classical approaches, and no methods were able to effectively 
address the two RNA protein-complexes included [7]. CASP needs a wide 
variety of RNA, DNA, and complexes as targets to see if this situation 
has changed. (This CASP category is conducted in close collaboration 
with RNApuzzles [8]).


Organic ligand-protein complexes: This area is of major importance for 
computer-aided drug discovery. Earlier, there have been community 
experiments to assess the accuracy of methods, particularly SAMPL, CSAR, 
D3R, and a new one, CACHE, has recently started (cache-challenge.org). 
These challenges have drawn strong international participation from 
researchers in both academia and industry. Here too, a number of 
promising deep learning papers have appeared, but in the 2022 CASP15 
pilot, classical methods were still superior [9]. So, we need 
appropriate targets to see if progress has been made since. Ideally, 
these should be sets of three-dimensional protein-ligand complexes from 
drug discovery projects, but single targets would also be appreciated. 
Additionally, where available, we will assess non-structural quantities 
such as affinities or affinity rankings and other properties of 
pharmaceutical interest when these are available (small molecule pKs, 
and DMPK related properties).


Ensembles of macromolecule conformations: It is now widely recognized 
that proteins and nucleic acids often adopt multiple conformations that 
can underpin their functions. In these cases, considering only a single 
protein or RNA conformation may be a significant oversimplification. The 
2022 CASP15 included a pilot experiment to assess methods for computing 
multiple conformations, with encouraging results [10], but with 
limitations imposed by the available experimental data. For 2024, we 
seek not only cases of 

[ccp4bb] Reminder: CBMS Lecture Series; Dessen, March 20.

[Stojanoff, Vivian]

You are cordially invited to join  the Center for Biomolecular Structure 
Lecture Series ………..





Andrea Dessen


CNRS Research Director


Institut de Biologie Structurale, France





WEDNESDAY, March 20, 13:30 (EDT)



"Architecture and Genomic Arrangement of Bacterial Cell Biosynthesis Complexes"



Register in advance for this meeting:


https://bnl.zoomgov.com/meeting/register/vJIsdOysqzoiHJzcKLSKZqX5jfwZQcIozkM



   Time conversion Link: 
https://www.worldtimebuddy.com/



Abstract: The bacterial cell wall is important for survival and shape, and its 
biosynthetic mechanism is the target of beta-lactam antibiotics. The spread of 
resistant strains, however, has limited the usefulness of these drugs and calls 
for efforts towards studies of cell wall formation that could lead to the 
development of innovative treatments. My group is interested in structurally 
and functionally characterizing protein complexes involved in both cytoplasmic 
and periplasmic steps of cell wall biosynthesis. The synthesis of 
peptidoglycan, the main component of the cell wall, starts in the cytoplasm, 
through sequential reactions catalyzed by Mur enzymes that have been suggested 
to associate into a multi-membered complex. This idea is supported by the 
observation that in many bacteria, mur genes are present in a single operon 
within the well conserved dcw cluster, and in some cases pairs of mur genes are 
fused to encode a single, chimeric polypeptide able to catalyze successive 
reactions. I will present the crystal structure of the MurE-MurF chimera from 
Bordetella pertussis, which reveals a head-to-tail, elongated architecture and 
indicates how sequential reactions could be catalyzed. In addition, I will also 
discuss structural details of complexes formed in the bacterial periplasm, 
notably between Penicillin-Binding Proteins (PBPs) and the scaffolding protein 
MreC, that act in partnership with Mur proteins in the cell wall biosynthesis 
process. These structural and functional insights shed light on the importance 
of studying pathways that are of critical relevance for bacterial cell survival 
in light of the antibiotic resistance crisis..



==



Vivian Stojanoff, PhD

Education, Training, Outreach

User Program

p 1(631) 344 8375

e lifescie...@bnl.gov

w https://www.bnl.gov/ps/lifesciences/



Address:

Center for Biomolecular Structure

National Synchrotron Light Source II

Building 745

Brookhaven National Laboratory

Upton NY 11973




Reply

Forward
CBMS Lecture Series - Andrea Dessen - March 20

(No subject)






To unsubscribe from the CCP4BB list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=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/

Re: [ccp4bb] Coot function - closest symmetry atom?

[Paul Emsley]

On 18/03/2024 10:26, Petr Pachl wrote:

--


Does anybody know if there is a function (or procedure) how to get info
about closest symmetry atom? For picking coot is performing something
like "Model atom pick (if failed) -> Symmetry atom pick", then it
returns to console and atom info at the bottom of the screen the found
atom. But can that be obtained in a function? My idea is to have a
shortcut "go to original atom based on symmetry related one".


Your second question is easier to answer than the first one - because it 
has been coded up already (in 2009). It's called "undo-symmetry-view" 
and all you need to do is bind it to a key. In fact, it's already bound 
to a key (Shift-V) if you have installed the key-bindings.


Paul.



To unsubscribe from the CCP4BB list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=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/

[ccp4bb] 2-year postdoctoral positio IBS Grenoble-France

[Carlos CONTRERAS-MARTEL]

Researcher in structural biology (w/m)

We have a funded 2-year postdoctoral position available in the 
Metalloproteins Unit at "Institut de biologie Structurale" (IBS) in 
Grenoble. The research will focus on the structural study of iron-sulfur 
(Fe-S) cluster biosynthesis in both prokaryotes and eukaryotes.


We are looking for a candidate with a Ph.D. in structural biology 
obtained less than 2 years ago, and proficiency in state-of-the-art 
cryoEM or X-ray crystallography software and techniques. More 
information about the position can be found here:


https://emploi.univ-grenoble-alpes.fr/job-offers/researcher-in-structural-biology-w-m--1396173.kjsp?RH=1681202200872

Don't hesite to contact us for more informations:
Mickaël Cherrier (mickael.cherr...@ibs.fr)
Yvain Nicolet (yvain.nico...@ibs.fr)


--
 Carlos CONTRERAS MARTEL, Ph.D.
 (CRHC CNRS)

 carlos.contreras-mar...@ibs.fr

 "Bacterial Pathogenesis Group"
Institut de Biologie Structurale
 UMR5075 CEA-CNRS-UGA

  IBS (PATBAC)
  Campus EPN
  71, avenue des Martyrs
  CS 10090
  38044 Grenoble CEDEX 9
  FRANCE


 tel : (+33) (0)4 57 42 86 41

http://www.ibs.fr/groupes/groupe-pathogenie-bacterienne/?lang=fr
http://www.ibs.fr/groups/bacterial-pathogenesis-group/?lang=en



To unsubscribe from the CCP4BB list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=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/

[ccp4bb] Coot function - closest symmetry atom?

[Petr Pachl]

Hi all.
Does anybody know if there is a function (or procedure) how to get info
about closest symmetry atom? For picking coot is performing something
like "Model atom pick (if failed) -> Symmetry atom pick", then it
returns to console and atom info at the bottom of the screen the found
atom. But can that be obtained in a function? My idea is to have a
shortcut "go to original atom based on symmetry related one".

Thanks a lot,
Petr

-- 
Petr Pachl PhD.
Structural Biology
Institute of Organic Chemistry and Biochemistry
Czech Academy of Sciences
Flemingovo n. 2
166 10 Prague 6
Czech Republic

office: + 420 220 183 210



To unsubscribe from the CCP4BB list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=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/