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Proteins, fundamental to cellular activities, reveal their function and evolution through their structure and sequence. CATH functional families (FunFams) are coherent clusters of protein domain sequences in which the function is conserved across their members. The increasing volume and complexity of protein data enabled by large-scale repositories like MGnify or AlphaFold Database requires more powerful approaches that can scale to the size of these new resources. In this work, we introduce MARC and FRAN, two algorithms developed to build upon and address limitations of GeMMA/FunFHMMER, our original methods developed to classify proteins with related functions using a hierarchical approach. We also present CATH-eMMA, which uses embeddings or Foldseek distances to form relationship trees from distance matrices, reducing computational demands and handling various data types effectively. CATH-eMMA offers a highly robust and much faster tool for clustering protein functions on a large scale, providing a new tool for future studies in protein function and evolution.
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Algoritmos , Bases de Datos de Proteínas , Proteínas , Proteínas/química , Proteínas/metabolismo , Análisis por Conglomerados , Biología Computacional/métodos , Dominios ProteicosRESUMEN
The COVID-19 disease is an ongoing global health concern. Although vaccination provides some protection, people are still susceptible to re-infection. Ostensibly, certain populations or clinical groups may be more vulnerable. Factors causing these differences are unclear and whilst socioeconomic and cultural differences are likely to be important, human genetic factors could influence susceptibility. Experimental studies indicate SARS-CoV-2 uses innate immune suppression as a strategy to speed-up entry and replication into the host cell. Therefore, it is necessary to understand the impact of variants in immunity-associated human proteins on susceptibility to COVID-19. In this work, we analysed missense coding variants in several SARS-CoV-2 proteins and their human protein interactors that could enhance binding affinity to SARS-CoV-2. We curated a dataset of 19 SARS-CoV-2: human protein 3D-complexes, from the experimentally determined structures in the Protein Data Bank and models built using AlphaFold2-multimer, and analysed the impact of missense variants occurring in the protein-protein interface region. We analysed 468 missense variants from human proteins and 212 variants from SARS-CoV-2 proteins and computationally predicted their impacts on binding affinities for the human viral protein complexes. We predicted a total of 26 affinity-enhancing variants from 13 human proteins implicated in increased binding affinity to SARS-CoV-2. These include key-immunity associated genes (TOMM70, ISG15, IFIH1, IFIT2, RPS3, PALS1, NUP98, AXL, ARF6, TRIMM, TRIM25) as well as important spike receptors (KREMEN1, AXL and ACE2). We report both common (e.g., Y13N in IFIH1) and rare variants in these proteins and discuss their likely structural and functional impact, using information on known and predicted functional sites. Potential mechanisms associated with immune suppression implicated by these variants are discussed. Occurrence of certain predicted affinity-enhancing variants should be monitored as they could lead to increased susceptibility and reduced immune response to SARS-CoV-2 infection in individuals/populations carrying them. Our analyses aid in understanding the potential impact of genetic variation in immunity-associated proteins on COVID-19 susceptibility and help guide drug-repurposing strategies.
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COVID-19 , Mutación Missense , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/inmunología , COVID-19/genética , COVID-19/virología , COVID-19/inmunología , Reposicionamiento de Medicamentos , Proteínas Virales/genética , Proteínas Virales/metabolismo , Unión Proteica , Predisposición Genética a la Enfermedad , Susceptibilidad a Enfermedades , Tratamiento Farmacológico de COVID-19RESUMEN
MOTIVATION: Protein domains are fundamental units of protein structure and play a pivotal role in understanding folding, function, evolution, and design. The advent of accurate structure prediction techniques has resulted in an influx of new structural data, making the partitioning of these structures into domains essential for inferring evolutionary relationships and functional classification. RESULTS: This article presents Chainsaw, a supervised learning approach to domain parsing that achieves accuracy that surpasses current state-of-the-art methods. Chainsaw uses a fully convolutional neural network which is trained to predict the probability that each pair of residues is in the same domain. Domain predictions are then derived from these pairwise predictions using an algorithm that searches for the most likely assignment of residues to domains given the set of pairwise co-membership probabilities. Chainsaw matches CATH domain annotations in 78% of protein domains versus 72% for the next closest method. When predicting on AlphaFold models, expert human evaluators were twice as likely to prefer Chainsaw's predictions versus the next best method. AVAILABILITY AND IMPLEMENTATION: github.com/JudeWells/Chainsaw.
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Algoritmos , Redes Neurales de la Computación , Dominios Proteicos , Proteínas , Proteínas/química , Bases de Datos de Proteínas , Biología Computacional/métodos , Programas Informáticos , HumanosRESUMEN
CATH (https://www.cathdb.info) classifies domain structures from experimental protein structures in the PDB and predicted structures in the AlphaFold Database (AFDB). To cope with the scale of the predicted data a new NextFlow workflow (CATH-AlphaFlow), has been developed to classify high-quality domains into CATH superfamilies and identify novel fold groups and superfamilies. CATH-AlphaFlow uses a novel state-of-the-art structure-based domain boundary prediction method (ChainSaw) for identifying domains in multi-domain proteins. We applied CATH-AlphaFlow to process PDB structures not classified in CATH and AFDB structures from 21 model organisms, expanding CATH by over 100%. Domains not classified in existing CATH superfamilies or fold groups were used to seed novel folds, giving 253 new folds from PDB structures (September 2023 release) and 96 from AFDB structures of proteomes of 21 model organisms. Where possible, functional annotations were obtained using (i) predictions from publicly available methods (ii) annotations from structural relatives in AFDB/UniProt50. We also predicted functional sites and highly conserved residues. Some folds are associated with important functions such as photosynthetic acclimation (in flowering plants), iron permease activity (in fungi) and post-natal spermatogenesis (in mice). CATH-AlphaFlow will allow us to identify many more CATH relatives in the AFDB, further characterising the protein structure landscape.
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ModelCIF (github.com/ihmwg/ModelCIF) is a data information framework developed for and by computational structural biologists to enable delivery of Findable, Accessible, Interoperable, and Reusable (FAIR) data to users worldwide. ModelCIF describes the specific set of attributes and metadata associated with macromolecular structures modeled by solely computational methods and provides an extensible data representation for deposition, archiving, and public dissemination of predicted three-dimensional (3D) models of macromolecules. It is an extension of the Protein Data Bank Exchange / macromolecular Crystallographic Information Framework (PDBx/mmCIF), which is the global data standard for representing experimentally-determined 3D structures of macromolecules and associated metadata. The PDBx/mmCIF framework and its extensions (e.g., ModelCIF) are managed by the Worldwide Protein Data Bank partnership (wwPDB, wwpdb.org) in collaboration with relevant community stakeholders such as the wwPDB ModelCIF Working Group (wwpdb.org/task/modelcif). This semantically rich and extensible data framework for representing computed structure models (CSMs) accelerates the pace of scientific discovery. Herein, we describe the architecture, contents, and governance of ModelCIF, and tools and processes for maintaining and extending the data standard. Community tools and software libraries that support ModelCIF are also described.
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Bases de Datos de Proteínas , Sustancias Macromoleculares/química , Conformación Proteica , Programas InformáticosRESUMEN
Protein kinases are important targets for treating human disorders, and they are the second most targeted families after G-protein coupled receptors. Several resources provide classification of kinases into evolutionary families (based on sequence homology); however, very few systematically classify functional families (FunFams) comprising evolutionary relatives that share similar functional properties. We have developed the FunFam-MARC (Multidomain ARchitecture-based Clustering) protocol, which uses multi-domain architectures of protein kinases and specificity-determining residues for functional family classification. FunFam-MARC predicts 2210 kinase functional families (KinFams), which have increased functional coherence, in terms of EC annotations, compared to the widely used KinBase classification. Our protocol provides a comprehensive classification for kinase sequences from >10,000 organisms. We associate human KinFams with diseases and drugs and identify 28 druggable human KinFams, i.e., enriched in clinically approved drugs. Since relatives in the same druggable KinFam tend to be structurally conserved, including the drug-binding site, these KinFams may be valuable for shortlisting therapeutic targets. Information on the human KinFams and associated 3D structures from AlphaFold2 are provided via our CATH FTP website and Zenodo. This gives the domain structure representative of each KinFam together with information on any drug compounds available. For 32% of the KinFams, we provide information on highly conserved residue sites that may be associated with specificity.
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Proteínas Quinasas , Proteínas , Humanos , Proteínas Quinasas/metabolismo , Proteínas/química , Bases de Datos de Proteínas , Homología de Secuencia de AminoácidoRESUMEN
Deep-learning (DL) methods like DeepMind's AlphaFold2 (AF2) have led to substantial improvements in protein structure prediction. We analyse confident AF2 models from 21 model organisms using a new classification protocol (CATH-Assign) which exploits novel DL methods for structural comparison and classification. Of ~370,000 confident models, 92% can be assigned to 3253 superfamilies in our CATH domain superfamily classification. The remaining cluster into 2367 putative novel superfamilies. Detailed manual analysis on 618 of these, having at least one human relative, reveal extremely remote homologies and further unusual features. Only 25 novel superfamilies could be confirmed. Although most models map to existing superfamilies, AF2 domains expand CATH by 67% and increases the number of unique 'global' folds by 36% and will provide valuable insights on structure function relationships. CATH-Assign will harness the huge expansion in structural data provided by DeepMind to rationalise evolutionary changes driving functional divergence.
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Furilfuramida , Proteínas , Humanos , Bases de Datos de Proteínas , Proteínas/químicaRESUMEN
MOTIVATION: CATH is a protein domain classification resource that exploits an automated workflow of structure and sequence comparison alongside expert manual curation to construct a hierarchical classification of evolutionary and structural relationships. The aim of this study was to develop algorithms for detecting remote homologues missed by state-of-the-art hidden Markov model (HMM)-based approaches. The method developed (CATHe) combines a neural network with sequence representations obtained from protein language models. It was assessed using a dataset of remote homologues having less than 20% sequence identity to any domain in the training set. RESULTS: The CATHe models trained on 1773 largest and 50 largest CATH superfamilies had an accuracy of 85.6 ± 0.4% and 98.2 ± 0.3%, respectively. As a further test of the power of CATHe to detect more remote homologues missed by HMMs derived from CATH domains, we used a dataset consisting of protein domains that had annotations in Pfam, but not in CATH. By using highly reliable CATHe predictions (expected error rate <0.5%), we were able to provide CATH annotations for 4.62 million Pfam domains. For a subset of these domains from Homo sapiens, we structurally validated 90.86% of the predictions by comparing their corresponding AlphaFold2 structures with structures from the CATH superfamilies to which they were assigned. AVAILABILITY AND IMPLEMENTATION: The code for the developed models is available on https://github.com/vam-sin/CATHe, and the datasets developed in this study can be accessed on https://zenodo.org/record/6327572. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Algoritmos , Proteínas , Humanos , Homología de Secuencia de Aminoácido , Proteínas/química , Bases de Datos de ProteínasRESUMEN
The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. Here, we report recent developments with InterPro (version 90.0) and its associated software, including updates to data content and to the website. These developments extend and enrich the information provided by InterPro, and provide a more user friendly access to the data. Additionally, we have worked on adding Pfam website features to the InterPro website, as the Pfam website will be retired in late 2022. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB. Moreover, we report the development of a card game as a method of engaging the non-scientific community. Finally, we discuss the benefits and challenges brought by the use of artificial intelligence for protein structure prediction.
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Bases de Datos de Proteínas , Humanos , Secuencia de Aminoácidos , Inteligencia Artificial , Internet , Proteínas/química , Programas InformáticosRESUMEN
Peripheral membrane proteins (PMPs) include a wide variety of proteins that have in common to bind transiently to the chemically complex interfacial region of membranes through their interfacial binding site (IBS). In contrast to protein-protein or protein-DNA/RNA interfaces, peripheral protein-membrane interfaces are poorly characterized. We collected a dataset of PMP domains representative of the variety of PMP functions: membrane-targeting domains (Annexin, C1, C2, discoidin C2, PH, PX), enzymes (PLA, PLC/D) and lipid-transfer proteins (START). The dataset contains 1328 experimental structures and 1194 AphaFold models. We mapped the amino acid composition and structural patterns of the IBS of each protein in this dataset, and evaluated which were more likely to be found at the IBS compared to the rest of the domains' accessible surface. In agreement with earlier work we find that about two thirds of the PMPs in the dataset have protruding hydrophobes (Leu, Ile, Phe, Tyr, Trp and Met) at their IBS. The three aromatic amino acids Trp, Tyr and Phe are a hallmark of PMPs IBS regardless of whether they protrude on loops or not. This is also the case for lysines but not arginines suggesting that, unlike for Arg-rich membrane-active peptides, the less membrane-disruptive lysine is preferred in PMPs. Another striking observation was the over-representation of glycines at the IBS of PMPs compared to the rest of their surface, possibly procuring IBS loops a much-needed flexibility to insert in-between membrane lipids. The analysis of the 9 superfamilies revealed amino acid distribution patterns in agreement with their known functions and membrane-binding mechanisms. Besides revealing novel amino acids patterns at protein-membrane interfaces, our work contributes a new PMP dataset and an analysis pipeline that can be further built upon for future studies of PMPs properties, or for developing PMPs prediction tools using for example, machine learning approaches.
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Membrana Celular , Péptidos , Aminoácidos/química , Sitios de Unión , Péptidos/química , Membrana Celular/químicaRESUMEN
While scientists can often infer the biological function of proteins from their 3-dimensional quaternary structures, the gap between the number of known protein sequences and their experimentally determined structures keeps increasing. A potential solution to this problem is presented by ever more sophisticated computational protein modeling approaches. While often powerful on their own, most methods have strengths and weaknesses. Therefore, it benefits researchers to examine models from various model providers and perform comparative analysis to identify what models can best address their specific use cases. To make data from a large array of model providers more easily accessible to the broader scientific community, we established 3D-Beacons, a collaborative initiative to create a federated network with unified data access mechanisms. The 3D-Beacons Network allows researchers to collate coordinate files and metadata for experimentally determined and theoretical protein models from state-of-the-art and specialist model providers and also from the Protein Data Bank.
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Metadatos , Registros , Secuencia de Aminoácidos , Bases de Datos de Proteínas , Simulación por ComputadorRESUMEN
The number of unique transmembrane (TM) protein structures doubled in the last four years, which can be attributed to the revolution of cryo-electron microscopy. In addition, AlphaFold2 (AF2) also provided a large number of predicted structures with high quality. However, if a specific protein family is the subject of a study, collecting the structures of the family members is highly challenging in spite of existing general and protein domain-specific databases. Here, we demonstrate this and assess the applicability and usability of automatic collection and presentation of protein structures via the ABC protein superfamily. Our pipeline identifies and classifies transmembrane ABC protein structures using the PFAM search and also aims to determine their conformational states based on special geometric measures, conftors. Since the AlphaFold database contains structure predictions only for single polypeptide chains, we performed AF2-Multimer predictions for human ABC half transporters functioning as dimers. Our AF2 predictions warn of possibly ambiguous interpretation of some biochemical data regarding interaction partners and call for further experiments and experimental structure determination. We made our predicted ABC protein structures available through a web application, and we joined the 3D-Beacons Network to reach the broader scientific community through platforms such as PDBe-KB.
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Transportadoras de Casetes de Unión a ATP , Furilfuramida , Transportadoras de Casetes de Unión a ATP/metabolismo , Inteligencia Artificial , Biología , Microscopía por Crioelectrón , Humanos , Modelos Moleculares , Conformación ProteicaRESUMEN
Experimental structures are leveraged through multiple sequence alignments, or more generally through homology-based inference (HBI), facilitating the transfer of information from a protein with known annotation to a query without any annotation. A recent alternative expands the concept of HBI from sequence-distance lookup to embedding-based annotation transfer (EAT). These embeddings are derived from protein Language Models (pLMs). Here, we introduce using single protein representations from pLMs for contrastive learning. This learning procedure creates a new set of embeddings that optimizes constraints captured by hierarchical classifications of protein 3D structures defined by the CATH resource. The approach, dubbed ProtTucker, has an improved ability to recognize distant homologous relationships than more traditional techniques such as threading or fold recognition. Thus, these embeddings have allowed sequence comparison to step into the 'midnight zone' of protein similarity, i.e. the region in which distantly related sequences have a seemingly random pairwise sequence similarity. The novelty of this work is in the particular combination of tools and sampling techniques that ascertained good performance comparable or better to existing state-of-the-art sequence comparison methods. Additionally, since this method does not need to generate alignments it is also orders of magnitudes faster. The code is available at https://github.com/Rostlab/EAT.
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Mutations in human proteins lead to diseases. The structure of these proteins can help understand the mechanism of such diseases and develop therapeutics against them. With improved deep learning techniques, such as RoseTTAFold and AlphaFold, we can predict the structure of proteins even in the absence of structural homologs. We modeled and extracted the domains from 553 disease-associated human proteins without known protein structures or close homologs in the Protein Databank. We noticed that the model quality was higher and the Root mean square deviation (RMSD) lower between AlphaFold and RoseTTAFold models for domains that could be assigned to CATH families as compared to those which could only be assigned to Pfam families of unknown structure or could not be assigned to either. We predicted ligand-binding sites, protein-protein interfaces and conserved residues in these predicted structures. We then explored whether the disease-associated missense mutations were in the proximity of these predicted functional sites, whether they destabilized the protein structure based on ddG calculations or whether they were predicted to be pathogenic. We could explain 80% of these disease-associated mutations based on proximity to functional sites, structural destabilization or pathogenicity. When compared to polymorphisms, a larger percentage of disease-associated missense mutations were buried, closer to predicted functional sites, predicted as destabilizing and pathogenic. Usage of models from the two state-of-the-art techniques provide better confidence in our predictions, and we explain 93 additional mutations based on RoseTTAFold models which could not be explained based solely on AlphaFold models.
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Mutación Missense , Proteínas , Bases de Datos de Proteínas , Humanos , Modelos Moleculares , Mutación , Proteínas/química , Proteínas/genéticaRESUMEN
BACKGROUND: Protein function prediction remains a key challenge. Domain composition affects protein function. Here we present DomFun, a Ruby gem that uses associations between protein domains and functions, calculated using multiple indices based on tripartite network analysis. These domain-function associations are combined at the protein level, to generate protein-function predictions. RESULTS: We analysed 16 tripartite networks connecting homologous superfamily and FunFam domains from CATH-Gene3D with functional annotations from the three Gene Ontology (GO) sub-ontologies, KEGG, and Reactome. We validated the results using the CAFA 3 benchmark platform for GO annotation, finding that out of the multiple association metrics and domain datasets tested, Simpson index for FunFam domain-function associations combined with Stouffer's method leads to the best performance in almost all scenarios. We also found that using FunFams led to better performance than superfamilies, and better results were found for GO molecular function compared to GO biological process terms. DomFun performed as well as the highest-performing method in certain CAFA 3 evaluation procedures in terms of [Formula: see text] and [Formula: see text] We also implemented our own benchmark procedure, Pathway Prediction Performance (PPP), which can be used to validate function prediction for additional annotations sources, such as KEGG and Reactome. Using PPP, we found similar results to those found with CAFA 3 for GO, moreover we found good performance for the other annotation sources. As with CAFA 3, Simpson index with Stouffer's method led to the top performance in almost all scenarios. CONCLUSIONS: DomFun shows competitive performance with other methods evaluated in CAFA 3 when predicting proteins function with GO, although results vary depending on the evaluation procedure. Through our own benchmark procedure, PPP, we have shown it can also make accurate predictions for KEGG and Reactome. It performs best when using FunFams, combining Simpson index derived domain-function associations using Stouffer's method. The tool has been implemented so that it can be easily adapted to incorporate other protein features, such as domain data from other sources, amino acid k-mers and motifs. The DomFun Ruby gem is available from https://rubygems.org/gems/DomFun . Code maintained at https://github.com/ElenaRojano/DomFun . Validation procedure scripts can be found at https://github.com/ElenaRojano/DomFun_project .
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Biología Computacional , Proteínas , Bases de Datos de Proteínas , Ontología de Genes , Anotación de Secuencia Molecular , Proteínas/genéticaRESUMEN
This article is dedicated to the memory of Cyrus Chothia, who was a leading light in the world of protein structure evolution. His elegant analyses of protein families and their mechanisms of structural and functional evolution provided important evolutionary and biological insights and firmly established the value of structural perspectives. He was a mentor and supervisor to many other leading scientists who continued his quest to characterise structure and function space. He was also a generous and supportive colleague to those applying different approaches. In this article we review some of his accomplishments and the history of protein structure classifications, particularly SCOP and CATH. We also highlight some of the evolutionary insights these two classifications have brought. Finally, we discuss how the expansion and integration of protein sequence data into these structural families helps reveal the dark matter of function space and can inform the emergence of novel functions in Metazoa. Since we cover 25 years of structural classification, it has not been feasible to review all structure based evolutionary studies and hence we focus mainly on those undertaken by the SCOP and CATH groups and their collaborators.
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The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. InterProScan is the underlying software that allows protein and nucleic acid sequences to be searched against InterPro's signatures. Signatures are predictive models which describe protein families, domains or sites, and are provided by multiple databases. InterPro combines signatures representing equivalent families, domains or sites, and provides additional information such as descriptions, literature references and Gene Ontology (GO) terms, to produce a comprehensive resource for protein classification. Founded in 1999, InterPro has become one of the most widely used resources for protein family annotation. Here, we report the status of InterPro (version 81.0) in its 20th year of operation, and its associated software, including updates to database content, the release of a new website and REST API, and performance improvements in InterProScan.
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Bases de Datos de Proteínas , Proteínas/química , Secuencia de Aminoácidos , COVID-19/metabolismo , Internet , Anotación de Secuencia Molecular , Dominios Proteicos , Mapas de Interacción de Proteínas , SARS-CoV-2/metabolismo , Alineación de SecuenciaRESUMEN
CATH (https://www.cathdb.info) identifies domains in protein structures from wwPDB and classifies these into evolutionary superfamilies, thereby providing structural and functional annotations. There are two levels: CATH-B, a daily snapshot of the latest domain structures and superfamily assignments, and CATH+, with additional derived data, such as predicted sequence domains, and functionally coherent sequence subsets (Functional Families or FunFams). The latest CATH+ release, version 4.3, significantly increases coverage of structural and sequence data, with an addition of 65,351 fully-classified domains structures (+15%), providing 500 238 structural domains, and 151 million predicted sequence domains (+59%) assigned to 5481 superfamilies. The FunFam generation pipeline has been re-engineered to cope with the increased influx of data. Three times more sequences are captured in FunFams, with a concomitant increase in functional purity, information content and structural coverage. FunFam expansion increases the structural annotations provided for experimental GO terms (+59%). We also present CATH-FunVar web-pages displaying variations in protein sequences and their proximity to known or predicted functional sites. We present two case studies (1) putative cancer drivers and (2) SARS-CoV-2 proteins. Finally, we have improved links to and from CATH including SCOP, InterPro, Aquaria and 2DProt.
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Biología Computacional/estadística & datos numéricos , Bases de Datos de Proteínas/estadística & datos numéricos , Dominios Proteicos , Proteínas/química , Secuencia de Aminoácidos , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/virología , Biología Computacional/métodos , Epidemias , Humanos , Internet , Anotación de Secuencia Molecular , Proteínas/genética , Proteínas/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiología , Análisis de Secuencia de Proteína/métodos , Homología de Secuencia de Aminoácido , Proteínas Virales/química , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
Genome3D consortium is a collaborative project involving protein structure prediction and annotation resources developed by six world-leading structural bioinformatics groups, based in the United Kingdom (namely Blundell, Murzin, Gough, Sternberg, Orengo, and Jones). The main objective of Genome3D serves as a common portal to provide both predicted models and annotations of proteins in model organisms, using several resources developed by these labs such as CATH-Gene3D, DOMSERF, pDomTHREADER, PHYRE, SUPERFAMILY, FUGUE/TOCATTA, and VIVACE. These resources primarily use SCOP- and/or CATH-based protein domain assignments. Another objective of Genome3D is to compare structural classifications of protein domains in CATH and SCOP databases and to provide a consensus mapping of CATH and SCOP protein superfamilies. CATH/SCOP mapping analyses led to the identification of total of 1429 consensus superfamilies.Currently, Genome3D provides structural annotations for ten model organisms, including Homo sapiens, Arabidopsis thaliana, Mus musculus, Escherichia coli, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Plasmodium falciparum, Staphylococcus aureus, and Schizosaccharomyces pombe. Thus, Genome3D serves as a common gateway to each structure prediction/annotation resource and allows users to perform comparative assessment of the predictions. It, thus, assists researchers to broaden their perspective on structure/function predictions of their query protein of interest in selected model organisms.
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Genómica/organización & administración , Bases del Conocimiento , Anotación de Secuencia Molecular/métodos , Proteoma/química , Animales , Arabidopsis , Genoma , Genómica/métodos , Humanos , Difusión de la Información , Alineación de Secuencia/métodos , Reino Unido , LevadurasRESUMEN
Genome3D (https://www.genome3d.eu) is a freely available resource that provides consensus structural annotations for representative protein sequences taken from a selection of model organisms. Since the last NAR update in 2015, the method of data submission has been overhauled, with annotations now being 'pushed' to the database via an API. As a result, contributing groups are now able to manage their own structural annotations, making the resource more flexible and maintainable. The new submission protocol brings a number of additional benefits including: providing instant validation of data and avoiding the requirement to synchronise releases between resources. It also makes it possible to implement the submission of these structural annotations as an automated part of existing internal workflows. In turn, these improvements facilitate Genome3D being opened up to new prediction algorithms and groups. For the latest release of Genome3D (v2.1), the underlying dataset of sequences used as prediction targets has been updated using the latest reference proteomes available in UniProtKB. A number of new reference proteomes have also been added of particular interest to the wider scientific community: cow, pig, wheat and mycobacterium tuberculosis. These additions, along with improvements to the underlying predictions from contributing resources, has ensured that the number of annotations in Genome3D has nearly doubled since the last NAR update article. The new API has also been used to facilitate the dissemination of Genome3D data into InterPro, thereby widening the visibility of both the annotation data and annotation algorithms.