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Catherine L.
Lawson
,
Andriy
Kryshtafovych
,
Grigore D.
Pintilie
,
Stephen
Burley
,
Jiří
Černý
,
Vincent B.
Chen
,
Paul
Emsley
,
Alberto
Gobbi
,
Andrzej
Joachimiak
,
Sigrid
Noreng
,
Michael G.
Prisant
,
Randy J.
Read
,
Jane S.
Richardson
,
Alexis L.
Rohou
,
Bohdan
Schneider
,
Benjamin D.
Sellers
,
Chenghua
Shao
,
Elizabeth
Sourial
,
Chris I.
Williams
,
Christopher J.
Williams
,
Ying
Yang
,
Venkat
Abbaraju
,
Pavel V.
Afonine
,
Matthew L.
Baker
,
Paul S.
Bond
,
Tom L.
Blundell
,
Tom
Burnley
,
Arthur
Campbell
,
Renzhi
Cao
,
Jianlin
Cheng
,
Grzegorz
Chojnowski
,
Kevin D.
Cowtan
,
Frank
Dimaio
,
Reza
Esmaeeli
,
Nabin
Giri
,
Helmut
Grubmüller
,
Soon Wen
Hoh
,
Jie
Hou
,
Corey F.
Hryc
,
Carola
Hunte
,
Maxim
Igaev
,
Agnel P.
Joseph
,
Wei-Chun
Kao
,
Daisuke
Kihara
,
Dilip
Kumar
,
Lijun
Lang
,
Sean
Lin
,
Sai R.
Maddhuri Venkata Subramaniya
,
Sumit
Mittal
,
Arup
Mondal
,
Nigel W.
Moriarty
,
Andrew
Muenks
,
Garib N.
Murshudov
,
Robert A.
Nicholls
,
Mateusz
Olek
,
Colin M.
Palmer
,
Alberto
Perez
,
Emmi
Pohjolainen
,
Karunakar R.
Pothula
,
Christopher N.
Rowley
,
Daipayan
Sarkar
,
Luisa U.
Schäfer
,
Christopher J.
Schlicksup
,
Gunnar F.
Schröder
,
Mrinal
Shekhar
,
Dong
Si
,
Abhishek
Singharoy
,
Oleg V.
Sobolev
,
Genki
Terashi
,
Andrea C.
Vaiana
,
Sundeep C.
Vedithi
,
Jacob
Verburgt
,
Xiao
Wang
,
Rangana
Warshamanage
,
Martyn
Winn
,
Simone
Weyand
,
Keitaro
Yamashita
,
Minglei
Zhao
,
Michael F.
Schmid
,
Helen M.
Berman
,
Wah
Chiu
Abstract: The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein–nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9–2.5 Å) resolution. Three published maps were selected as targets: Escherichia coli beta-galactosidase with inhibitor, SARS-CoV-2 virus RNA-dependent RNA polymerase with covalently bound nucleotide analog and SARS-CoV-2 virus ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. The quality of submitted ligand models and surrounding atoms were analyzed by visual inspection and quantification of local map quality, model-to-map fit, geometry, energetics and contact scores. A composite rather than a single score was needed to assess macromolecule+ligand model quality. These observations lead us to recommend best practices for assessing cryo-EM structures of liganded macromolecules reported at near-atomic resolution.
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Jun 2024
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Open Access
Abstract: The results of tertiary structure assessment at CASP15 are reported. For the first time, recognizing the outstanding performance of AlphaFold 2 (AF2) at CASP14, all single-chain predictions were assessed together, irrespective of whether a template was available. At CASP15, there was no single stand-out group, with most of the best-scoring groups—led by PEZYFoldings, UM-TBM, and Yang Server—employing AF2 in one way or another. Many top groups paid special attention to generating deep Multiple Sequence Alignments (MSAs) and testing variant MSAs, thereby allowing them to successfully address some of the hardest targets. Such difficult targets, as well as lacking templates, were typically proteins with few homologues. Local divergence between prediction and target correlated with localization at crystal lattice or chain interfaces, and with regions exhibiting high B-factor factors in crystal structure targets, and should not necessarily be considered as representing error in the prediction. However, analysis of exposed and buried side chain accuracy showed room for improvement even in the latter. Nevertheless, a majority of groups produced high-quality predictions for most targets, which are valuable for experimental structure determination, functional analysis, and many other tasks across biology. These include those applying methods similar to those used to generate major resources such as the AlphaFold Protein Structure Database and the ESM Metagenomic atlas: the confidence estimates of the former were also notably accurate.
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Sep 2023
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VMXm-Versatile Macromolecular Crystallography microfocus
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Leila T.
Alexander
,
Janani
Durairaj
,
Andriy
Kryshtafovych
,
Luciano A.
Abriata
,
Yusupha
Bayo
,
Gira
Bhabha
,
Cécile
Breyton
,
Simon G.
Caulton
,
James
Chen
,
Séraphine
Degroux
,
Damian C.
Ekiert
,
Benedikte S.
Erlandsen
,
Peter L.
Freddolino
,
Dominic
Gilzer
,
Chris
Greening
,
Jonathan M.
Grimes
,
Rhys
Grinter
,
Manickam
Gurusaran
,
Marcus D.
Hartmann
,
Charlie J.
Hitchman
,
Jeremy R.
Keown
,
Ashleigh
Kropp
,
Petri
Kursula
,
Andrew L.
Lovering
,
Bruno
Lemaitre
,
Andrea
Lia
,
Shiheng
Liu
,
Maria
Logotheti
,
Shuze
Lu
,
Sigurbjorn
Markusson
,
Mitchell D.
Miller
,
George
Minasov
,
Hartmut H.
Niemann
,
Felipe
Opazo
,
George N.
Phillips
,
Owen R.
Davies
,
Samuel
Rommelaere
,
Monica
Rosas‐lemus
,
Pietro
Roversi
,
Karla
Satchell
,
Nathan
Smith
,
Mark A.
Wilson
,
Kuan‐lin
Wu
,
Xian
Xia
,
Han
Xiao
,
Wenhua
Zhang
,
Z. Hong
Zhou
,
Krzysztof
Fidelis
,
Maya
Topf
,
John
Moult
,
Torsten
Schwede
Diamond Proposal Number(s):
[19946, 23570, 27314, 28534]
Open Access
Abstract: We present an in-depth analysis of selected CASP15 targets, focusing on their biological and functional significance. The authors of the structures identify and discuss key protein features and evaluate how effectively these aspects were captured in the submitted predictions. While the overall ability to predict three-dimensional protein structures continues to impress, reproducing uncommon features not previously observed in experimental structures is still a challenge. Furthermore, instances with conformational flexibility and large multimeric complexes highlight the need for novel scoring strategies to better emphasize biologically relevant structural regions. Looking ahead, closer integration of computational and experimental techniques will play a key role in determining the next challenges to be unraveled in the field of structural molecular biology.
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Jul 2023
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I03-Macromolecular Crystallography
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Leila T.
Alexander
,
Rosalba
Lepore
,
Andriy
Kryshtafovych
,
Athanasios
Adamopoulos
,
Markus
Alahuhta
,
Ann M.
Arvin
,
Yannick J.
Bomble
,
Bettina
Böttcher
,
Cécile
Breyton
,
Valerio
Chiarini
,
Naga Babu
Chinnam
,
Wah
Chiu
,
Krzysztof
Fidelis
,
Rhys
Grinter
,
Gagan D.
Gupta
,
Marcus D.
Hartmann
,
Christopher S.
Hayes
,
Tatjana
Heidebrecht
,
Andrea
Ilari
,
Andrzej
Joachimiak
,
Youngchang
Kim
,
Romain
Linares
,
Andrew L.
Lovering
,
Vladimir V.
Lunin
,
Andrei N.
Lupas
,
Cihan
Makbul
,
Karolina
Michalska
,
John
Moult
,
Prasun K.
Mukherjee
,
William
Nutt
,
Stefan L.
Oliver
,
Anastassis
Perrakis
,
Lucy
Stols
,
John A.
Tainer
,
Maya
Topf
,
Susan E.
Tsutakawa
,
Mauricio
Valdivia‐delgado
,
Torsten
Schwede
Open Access
Abstract: The biological and functional significance of selected Critical Assessment of Techniques for Protein Structure Prediction 14 (CASP14) targets are described by the authors of the structures. The authors highlight the most relevant features of the target proteins and discuss how well these features were reproduced in the respective submitted predictions. The overall ability to predict three-dimensional structures of proteins has improved remarkably in CASP14, and many difficult targets were modeled with impressive accuracy. For the first time in the history of CASP, the experimentalists not only highlighted that computational models can accurately reproduce the most critical structural features observed in their targets, but also envisaged that models could serve as a guidance for further studies of biologically-relevant properties of proteins.
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Dec 2021
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Open Access
Abstract: We report here an assessment of the model refinement category of the 14th round of Critical Assessment of Structure Prediction (CASP14). As before, predictors submitted up to five ranked refinements, along with associated residue-level error estimates, for targets that had a wide range of starting quality. The ability of groups to accurately rank their submissions and to predict coordinate error varied widely. Overall only four groups out-performed a “naïve predictor” corresponding to resubmission of the starting model. Among the top groups there are interesting differences of approach and in the spread of improvements seen: some methods are more conservative, others more adventurous. Some targets were “double-barrelled” for which predictors were offered a high-quality AlphaFold 2 (AF2)-derived prediction alongside another of lower quality. The AF2-derived models were largely unimprovable, many of their apparent errors being found to reside at domain and, especially, crystal lattice contacts. Refinement is shown to have a mixed impact overall on structure-based function annotation methods to predict nucleic acid binding, spot catalytic sites and dock protein structures.
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Jul 2021
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I02-Macromolecular Crystallography
I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
I04-Macromolecular Crystallography
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Rosalba
Lepore
,
Andriy
Kryshtafovych
,
Markus
Alahuhta
,
Harshul A.
Veraszto
,
Yannick J.
Bomble
,
Joshua C.
Bufton
,
Alex N.
Bullock
,
Cody
Caba
,
Hongnan
Cao
,
Owen R.
Davies
,
Ambroise
Desfosses
,
Matthew
Dunne
,
Krzysztof
Fidelis
,
Celia W.
Goulding
,
Manickam
Gurusaran
,
Irina
Gutsche
,
Christopher J.
Harding
,
Marcus D.
Hartmann
,
Christopher S.
Hayes
,
Andrzej
Joachimiak
,
Petr G.
Leiman
,
Peter
Loppnau
,
Andrew L.
Lovering
,
Vladimir V.
Lunin
,
Karolina
Michalska
,
Ignacio
Mir‐sanchis
,
Alok
Mitra
,
John
Moult
,
George N.
Phillips Jr
,
Daniel
Pinkas
,
Phoebe A.
Rice
,
Yufeng
Tong
,
Maya
Topf
,
Jonathan D.
Walton
,
Torsten
Schwede
Diamond Proposal Number(s):
[14692]
Open Access
Abstract: The functional and biological significance of selected CASP13 targets are described by the authors of the structures. The structural biologists discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP13 experiment.
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Sep 2019
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I03-Macromolecular Crystallography
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Andriy
Kryshtafovych
,
John
Moult
,
Arnaud
Basle
,
Alex
Burgin
,
Timothy K.
Craig
,
Robert A.
Edwards
,
Deborah
Fass
,
Marcus
Hartmann
,
Mateusz
Korycinski
,
Rick
Lewis
,
Donald
Lorimer
,
Andrei N.
Lupas
,
Janet
Newman
,
Thomas S.
Peat
,
Kurt H.
Piepenbrink
,
Janani
Prahlad
,
Mark
Van Raaij
,
Forest
Rohwer
,
Anca M.
Segall
,
Victor
Seguritan
,
Eric J.
Sundberg
,
Abhimanyu
Singh
,
Mark A.
Wilson
,
Torsten
Schwede
Diamond Proposal Number(s):
[9948]
Open Access
Abstract: The Critical Assessment of protein Structure Prediction (CASP) experiment would not have been possible without the prediction targets provided by the experimental structural biology community. In this article, selected crystallographers providing targets for the CASP11 experiment discuss the functional and biological significance of the target proteins, highlight their most interesting structural features and assess whether these features were correctly reproduced in the predictions submitted to CASP11.
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Oct 2015
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