Comparative evaluation of AlphaFold2 and disorder predictors for prediction of intrinsic disorder, disorder content and fully disordered proteins DOI Creative Commons
Bi Zhao,

Sina Ghadermarzi,

Lukasz Kurgan

и другие.

Computational and Structural Biotechnology Journal, Год журнала: 2023, Номер 21, С. 3248 - 3258

Опубликована: Янв. 1, 2023

We expand studies of AlphaFold2 (AF2) in the context intrinsic disorder prediction by comparing it against a broad selection 20 accurate, popular and recently released predictors. use 25% larger benchmark dataset with 646 proteins cover protein-level predictions content fully disordered proteins. AF2-based secure relatively high Area Under receiver operating characteristic Curve (AUC) 0.77 are statistically outperformed several modern predictors that AUCs around 0.8 median runtime about s compared to 1200 for AF2. Moreover, AF2 provides modestly accurate (F1 = 0.59 vs. 0.91 best predictor) (mean absolute error 0.21 0.15). also generates more 20% have short sequences few regions tend be located at sequence termini, which absent protein-binding regions. Interestingly, most rely on deep neural networks, suggesting these models useful protein structure predictions.

Язык: Английский

Conformational ensembles of the human intrinsically disordered proteome DOI
Giulio Tesei, Anna Ida Trolle, Nicolas Jonsson

и другие.

Nature, Год журнала: 2024, Номер 626(8000), С. 897 - 904

Опубликована: Янв. 31, 2024

Язык: Английский

Процитировано

141
MobiDB: 10 years of intrinsically disordered proteins DOI Creative Commons
Damiano Piovesan, Alessio Del Conte, Damiano Clementel

и другие.

Nucleic Acids Research, Год журнала: 2022, Номер 51(D1), С. D438 - D444

Опубликована: Ноя. 23, 2022

Abstract The MobiDB database (URL: https://mobidb.org/) is a knowledge base of intrinsically disordered proteins. aggregates disorder annotations derived from the literature and experimental evidence along with predictions for all known protein sequences. generates new captures functional significance regions by processing combining complementary sources information. Since its first release 10 years ago, has evolved in order to improve quality coverage accessibility. now reached maturity terms data standardization visualization. Here, we present which focuses on optimization user experience content. major advances compared previous version are integration AlphaFoldDB re-implementation homology transfer pipeline, expands manually curated two orders magnitude. Finally, entry page been restyled provide an overview available separate views that highlight structural functions associated different binding modes.

Язык: Английский

Процитировано

129
Systematic identification of conditionally folded intrinsically disordered regions by AlphaFold2 DOI Creative Commons
T. Reid Alderson, Iva Pritišanac, Đesika Kolarić

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(44)

Опубликована: Окт. 25, 2023

The AlphaFold Protein Structure Database contains predicted structures for millions of proteins. For the majority human proteins that contain intrinsically disordered regions (IDRs), which do not adopt a stable structure, it is generally assumed these have low AlphaFold2 confidence scores reflect low-confidence structural predictions. Here, we show assigns confident to nearly 15% IDRs. By comparison experimental NMR data subset IDRs are known conditionally fold (i.e., upon binding or under other specific conditions), find often predicts structure folded state. Based on databases fold, estimate can identify folding at precision as high 88% 10% false positive rate, remarkable considering IDR were minimally represented in its training data. We disease mutations fivefold enriched over general and up 80% prokaryotes compared less than 20% eukaryotic These results indicate large proteomes eukaryotes function absence conditional folding, but acquire folds more sensitive mutations. emphasize predictions reveal functionally relevant plasticity within cannot offer realistic ensemble representations

Язык: Английский

Процитировано

129
AlphaFold2: A Role for Disordered Protein/Region Prediction? DOI Open Access
Carter J. Wilson, Wing‐Yiu Choy, Mikko Karttunen

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(9), С. 4591 - 4591

Опубликована: Апрель 21, 2022

The development of AlphaFold2 marked a paradigm-shift in the structural biology community. Herein, we assess ability to predict disordered regions against traditional sequence-based disorder predictors. We find that performs well at discriminating regions, but also note predictor one constructs from an structure determines accuracy. In particular, naïve, non-trivial assumption residues assigned helices, strands, and H-bond stabilized turns are likely ordered all other results dramatic overestimation disorder; conversely, predicted local distance difference test (pLDDT) provides excellent measure residue-wise disorder. Furthermore, by employing molecular dynamics (MD) simulations, interesting relationship between pLDDT secondary structure, may explain our observations suggests broader application for characterizing intrinsically proteins (IDPs/IDRs).

Язык: Английский

Процитировано

122
Intrinsic protein disorder and conditional folding in AlphaFoldDB DOI Creative Commons
Damiano Piovesan, Alexander Miguel Monzón, Silvio C. E. Tosatto

и другие.

Protein Science, Год журнала: 2022, Номер 31(11)

Опубликована: Окт. 10, 2022

Abstract Intrinsically disordered regions (IDRs) defying the traditional protein structure–function paradigm have been difficult to analyze. The availability of accurate structure predictions on a large scale in AlphaFoldDB offers fresh perspective IDR prediction. Here, we establish three baselines for prediction from models based recent CAID dataset. Surprisingly, is highly competitive predicting both IDRs and conditionally folded binding regions, demonstrating plasticity disorder continuum.

Язык: Английский

Процитировано

101
The HIV capsid mimics karyopherin engagement of FG-nucleoporins DOI Creative Commons
Claire F. Dickson, Sophie Hertel, Andrew Tuckwell

и другие.

Nature, Год журнала: 2024, Номер unknown

Опубликована: Янв. 24, 2024

Abstract HIV can infect non-dividing cells because the viral capsid overcome selective barrier of nuclear pore complex and deliver genome directly into nucleus 1,2 . Remarkably, intact is more than 1,000 times larger size limit prescribed by diffusion 3 This in central channel composed intrinsically disordered nucleoporin domains enriched phenylalanine–glycine (FG) dipeptides. Through multivalent FG interactions, cellular karyopherins their bound cargoes solubilize this phase to drive nucleocytoplasmic transport 4 By performing an vitro dissection complex, we show that a pocket on surface similarly interacts with motifs from multiple nucleoporins interaction licences capsids penetrate FG-nucleoporin condensates. karyopherin mimicry model addresses key conceptual challenge for role entry offers explanation as how exogenous entity much any known cargo may be able non-destructively breach envelope.

Язык: Английский

Процитировано

59
AlphaFold2 Can Predict Single-Mutation Effects DOI
J. Michael McBride, Konstantin Polev,

Amirbek Abdirasulov

и другие.

Physical Review Letters, Год журнала: 2023, Номер 131(21)

Опубликована: Ноя. 20, 2023

AlphaFold2 (AF) is a promising tool, but it accurate enough to predict single mutation effects? Here, we report that the localized structural deformation between protein pairs differing by only 1-3 mutations-as measured effective strain-is correlated across 3901 experimental and AF-predicted structures. Furthermore, analysis of ∼11 000 proteins shows local change correlates with various phenotypic changes. These findings suggest AF can range magnitude single-mutation effects on average, propose method improve precision predictions indicate when are unreliable.

Язык: Английский

Процитировано

53
Critical assessment of protein intrinsic disorder prediction (CAID) ‐ Results of round 2 DOI Creative Commons
Alessio Del Conte, Mahta Mehdiabadi,

Adel Bouhraoua

и другие.

Proteins Structure Function and Bioinformatics, Год журнала: 2023, Номер 91(12), С. 1925 - 1934

Опубликована: Авг. 25, 2023

Protein intrinsic disorder (ID) is a complex and context-dependent phenomenon that covers continuum between fully disordered states folded with long dynamic regions. The lack of ground truth fits all ID flavors the potential for order-to-disorder transitions depending on specific conditions makes prediction challenging. CAID2 challenge aimed to evaluate performance different methods across benchmarks, leveraging annotation provided by DisProt database, which stores coordinates regions when there experimental evidence in literature. demonstrated varying highlighting need continued development more versatile efficient software. Depending application, researchers may balance execution time selecting predictor. Methods based AlphaFold2 seem be good predictors but they are better at detecting absence order rather than as defined DisProt. can freely used through CAID Prediction Portal, has been integrated into OpenEBench, will become official platform running future challenges.

Язык: Английский

Процитировано

45
The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins DOI
Vinayak Agarwal, Andrew C. McShan

Nature Chemical Biology, Год журнала: 2024, Номер 20(8), С. 950 - 959

Опубликована: Июнь 21, 2024

Язык: Английский

Процитировано

32
The origin and structural evolution of de novo genes in Drosophila DOI Creative Commons
Junhui Peng, Li Zhao

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 27, 2024

Abstract Recent studies reveal that de novo gene origination from previously non-genic sequences is a common mechanism for innovation. These young genes provide an opportunity to study the structural and functional origins of proteins. Here, we combine high-quality base-level whole-genome alignments computational modeling origination, evolution, protein structures lineage-specific genes. We identify 555 candidates in D. melanogaster originated within Drosophilinae lineage. Sequence composition, evolutionary rates, expression patterns indicate possible gradual or adaptive shifts with their ages. Surprisingly, find little overall changes several potentially well-folded structures. Ancestral sequence reconstruction analysis reveals most are often born well-folded. Single-cell RNA-seq testis shows although enriched spermatocytes, biased towards early spermatogenesis stage, indicating important but less emphasized roles germline cells testis. This provides systematic overview origin, -specific

Язык: Английский

Процитировано

28