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المؤلفون: Maria-Evangelia Karyadi, Julian M. Schmidt-Engler, Carlo Camilloni, Sammy H. S. Chan, Anaïs M. E. Cassaignau, Michele Vendruscolo, Lisa D. Cabrita, Anne S. Wentink, Christopher A. Waudby, John Christodoulou, Tomasz Wlodarski
المصدر: Proceedings of the National Academy of Sciences of the United States of America
مصطلحات موضوعية: Models, Molecular, 0301 basic medicine, Protein Folding, Magnetic Resonance Spectroscopy, Filamins, Isomerase, Filamin, Ribosome, Domain (software engineering), 03 medical and health sciences, chemistry.chemical_compound, Biosynthesis, Protein biosynthesis, Humans, protein misfolding, Proteostasis Deficiencies, Multidisciplinary, molecular dynamics simulations, Biological Sciences, Folding (chemistry), Biophysics and Computational Biology, nuclear magnetic resonance, Kinetics, 030104 developmental biology, chemistry, Tandem Repeat Sequences, tandem repeat protein, Biophysics, Thermodynamics, cotranslational folding, Protein folding, Ribosomes, Protein Modification, Translational
الوصف: Significance Efficient synthesis and folding of proteins, avoiding misfolded states, are central to cell function. As folding may be initiated in parallel with translation, key experimental challenges are to map changes that occur in folding free energy landscapes as translation proceeds and to understand how these landscapes might be modulated by the ribosome and auxiliary factors. Here, we study the length-dependent folding of a domain from a tandem repeat protein and solve the structure of a stable folding intermediate. Although destabilized by the ribosome at equilibrium, modeling of the nonequilibrium folding pathway nevertheless indicates a significant role for proline isomerization during translation. We develop a simple model to explore the impact of cotranslational folding kinetics on misfolding hazards.
Cotranslational folding (CTF) is a fundamental molecular process that ensures efficient protein biosynthesis and minimizes the formation of misfolded states. However, the complexity of this process makes it extremely challenging to obtain structural characterizations of CTF pathways. Here, we correlate observations of translationally arrested nascent chains with those of a systematic C-terminal truncation strategy. We create a detailed description of chain length-dependent free energy landscapes associated with folding of the FLN5 filamin domain, in isolation and on the ribosome, and thus, quantify a substantial destabilization of the native structure on the ribosome. We identify and characterize two folding intermediates formed in isolation, including a partially folded intermediate associated with the isomerization of a conserved cis proline residue. The slow folding associated with this process raises the prospect that neighboring unfolded domains might accumulate and misfold during biosynthesis. We develop a simple model to quantify the risk of misfolding in this situation and show that catalysis of folding by peptidyl-prolyl isomerases is sufficient to eliminate this hazard.URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f78ba1add2d83a3e2d60f4afc439352e
https://doi.org/10.1073/pnas.1716252115 -
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المؤلفون: Guido Tiana, Carlo Camilloni, Michele Vendruscolo, Andrea Possenti
المساهمون: Tiana, Guido [0000-0001-9868-1809], Apollo - University of Cambridge Repository
المصدر: Proteins: Structure, Function, and Bioinformatics. 86:956-964
مصطلحات موضوعية: Models, Molecular, 0301 basic medicine, Protein Folding, Protein Conformation, Computer science, Computational biology, Information theory, Intrinsically disordered proteins, information content, Biochemistry, 03 medical and health sciences, Protein structure, Protein sequencing, Structural Biology, Amino Acid Sequence, Molecular Biology, Peptide sequence, Sequence (medicine), designed proteins, 030102 biochemistry & molecular biology, protein folding/function, Computational Biology, Proteins, Biomolecules (q-bio.BM), Genetic code, structure prediction, 030104 developmental biology, Quantitative Biology - Biomolecules, FOS: Biological sciences, Thermodynamics, Protein folding, intrinsically disordered proteins
الوصف: Proteins employ the information stored in the genetic code and translated into their sequences to carry out well-defined functions in the cellular environment. The possibility to encode for such functions is controlled by the balance between the amount of information supplied by the sequence and that left after that the protein has folded into its structure. We developed a computational algorithm to evaluate the amount of information necessary to specify the protein structure, keeping into account the thermodynamic properties of protein folding. We thus show that the information remaining in the protein sequence after encoding for its structure (the 'information gap') is very close to what needed to encode for its function and interactions. Then, by predicting the information gap directly from the protein sequence, we show that it may be possible to use these insights from information theory to discriminate between ordered and disordered proteins, to identify unknown functions, and to optimize designed proteins sequences.
وصف الملف: application/pdf
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المؤلفون: Alessandra Pesce, Marco Orlando, Stefania Brocca, Marina Lotti, Sandra Pucciarelli, Marco Nardini, Michela Lapi, Alberto Barbiroli, Carlo Camilloni, Marco Mangiagalli, Serena Maione
المساهمون: Mangiagalli, M, Lapi, M, Maione, S, Orlando, M, Brocca, S, Pesce, A, Barbiroli, A, Camilloni, C, Pucciarelli, S, Lotti, M, Nardini, M
مصطلحات موضوعية: 0301 basic medicine, Models, Molecular, Protein Conformation, alpha-Helical, cooperativity, Gene Expression, Crystallography, X-Ray, Biochemistry, Substrate Specificity, 0302 clinical medicine, psychrophilic enzyme, Enzyme Stability, glycoside hydrolase, Cloning, Molecular, Psychrophile, Marinomonas, Phylogeny, chemistry.chemical_classification, computer.file_format, Recombinant Proteins, Cold Temperature, enzyme kinetic, 030220 oncology & carcinogenesis, Thermodynamics, Mesophile, Protein Binding, Genetic Vectors, Antarctic Regions, 03 medical and health sciences, Bacterial Proteins, Escherichia coli, Protein Interaction Domains and Motifs, Amino Acid Sequence, Thermolabile, Protein Structure, Quaternary, Molecular Biology, Binding Sites, Sequence Homology, Amino Acid, Thermophile, Substrate (chemistry), Galactose, Cell Biology, Protein Data Bank, beta-Galactosidase, Protein Structure, Tertiary, Kinetics, 030104 developmental biology, Enzyme, chemistry, cold adaptation, Biophysics, Protein quaternary structure, Protein Conformation, beta-Strand, Protein Multimerization, computer, Sequence Alignment
الوصف: To survive in cold environments, psychrophilic organisms produce enzymes endowed with high specific activity at low temperature. The structure of these enzymes is usually flexible and mostly thermolabile. In this work, we investigate the structural basis of cold adaptation of a GH42 β-galactosidase from the psychrophilic Marinomonas ef1. This enzyme couples cold activity with astonishing robustness for a psychrophilic protein, for it retains 23% of its highest activity at 5°C and it is stable for several days at 37°C and even 50°C. Phylogenetic analyses indicate a close relationship with thermophilic β-galactosidases, suggesting that the present-day enzyme evolved from a thermostable scaffold modeled by environmental selective pressure. The crystallographic structure reveals the overall similarity with GH42 enzymes, along with a hexameric arrangement (dimer of trimers) not found in psychrophilic, mesophilic, and thermophilic homologues. In the quaternary structure, protomers form a large central cavity, whose accessibility to the substrate is promoted by the dynamic behavior of surface loops, even at low temperature. A peculiar cooperative behavior of the enzyme is likely related to the increase of the internal cavity permeability triggered by heating. Overall, our results highlight a novel strategy of enzyme cold adaptation, based on the oligomerization state of the enzyme, which effectively challenges the paradigm of cold activity coupled with intrinsic thermolability. DATABASE: Structural data are available in the Protein Data Bank database under the accession number 6Y2K.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::377881be43c22122ddeaef1692e1af46
http://hdl.handle.net/10281/276684 -
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المؤلفون: B. Pavel, L. Vittorio, C. Michele, F. Marta, W. Andrew, G. Federico, V. Michele, Š. Jiří, Davide Provasi, M. Layla, K. Evgeny, S. Matteo, V. Omar, Riccardo Capelli, M. Carla, David W.H. Swenson, Kim E. Jelfs, G. Piero, D. Davide, M. Angelos, P. Jim, Gareth A. Tribello, M. Fabrizio, C. Francesco, P. Michele, E. Bernd, Cristina Paissoni, M. Matteo, F. Haohao, L. Kresten, P. Pablo, T. Pratyush, L. Alessandro, Marco De La Pierre, B. Mattia, J. Alexander, M. Tetsuya, B. Sandro, Andrew L. Ferguson, Gabriella T. Heller, Francesco Luigi Gervasio, B. Davide, R. Paolo, D. Viktor, Massimiliano Bonomi, I. Michele, Peter G. Bolhuis, P. GiovanniMaria, Carlo Camilloni, C. Andrea, P. Elena, S. Vojtěch, James S. Fraser, L. Thomas, C. Haochuan, C. Paolo, N. Marco, B. Alessandro, P. Fabio, B. Giovanni, I. Marcella, G. Alejandro, C. Wei, Glen M. Hocky, G. Toni, P. Adriana, Gabriele C. Sosso, Q. David, P. Silvio, Gregory A. Voth, M. Ralf, R. Stefano, D. Sandip, R. Jakub
المساهمون: The Royal Society, Département de Biologie structurale et Chimie - Department of Structural Biology and Chemistry, Institut Pasteur [Paris] (IP), Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Scuola Internazionale Superiore di Studi Avanzati / International School for Advanced Studies (SISSA / ISAS), Università degli Studi di Milano = University of Milan (UNIMI), Queen's University [Belfast] (QUB), Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Blaise Pascal (CBP), École normale supérieure de Lyon (ENS de Lyon), University of Rochester [USA], Bonomi, M., Bussi, G., Camilloni, C., Tribello, G. A., Banas, P., Barducci, A., Bernetti, M., Bolhuis, P. G., Bottaro, S., Branduardi, D., Capelli, R., Carloni, P., Ceriotti, M., Cesari, A., Chen, H., Chen, W., Colizzi, F., De, S., De La Pierre, M., Donadio, D., Drobot, V., Ensing, B., Ferguson, A. L., Filizola, M., Fraser, J. S., Fu, H., Gasparotto, P., Gervasio, F. L., Giberti, F., Gil-Ley, A., Giorgino, T., Heller, G. T., Hocky, G. M., Iannuzzi, M., Invernizzi, M., Jelfs, K. E., Jussupow, A., Kirilin, E., Laio, A., Limongelli, V., Lindorff-Larsen, K., Lohr, T., Marinelli, F., Martin-Samos, L., Masetti, M., Meyer, R., Michaelides, A., Molteni, C., Morishita, T., Nava, M., Paissoni, C., Papaleo, E., Parrinello, M., Pfaendtner, J., Piaggi, P., Piccini, G. M., Pietropaolo, A., Pietrucci, F., Pipolo, S., Provasi, D., Quigley, D., Raiteri, P., Raniolo, S., Rydzewski, J., Salvalaglio, M., Sosso, G. C., Spiwok, V., Sponer, J., Swenson, D. W. H., Tiwary, P., Valsson, O., Vendruscolo, M., Voth, G. A., White, A., Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano [Milano] (UNIMI), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille, École normale supérieure - Lyon (ENS Lyon), Simulation of Biomolecular Systems (HIMS, FNWI), Molecular Simulations (HIMS, FNWI), Massimiliano Bonomi, Giovanni Bussi, Carlo Camilloni, Gareth A. Tribello, Pavel Banáš, Alessandro Barducci, Mattia Bernetti, Peter G. Bolhuis, Sandro Bottaro, Davide Branduardi, Riccardo Capelli, Paolo Carloni, Michele Ceriotti, Andrea Cesari, Haochuan Chen, Wei Chen, Francesco Colizzi, Sandip De, Marco De La Pierre, Davide Donadio, Viktor Drobot, Bernd Ensing, Andrew L. Ferguson, Marta Filizola, James S. Fraser, Haohao Fu, Piero Gasparotto, Francesco Luigi Gervasio, Federico Giberti, Alejandro Gil-Ley, Toni Giorgino, Gabriella T. Heller, Glen M. Hocky, Marcella Iannuzzi, Michele Invernizzi, Kim E. Jelfs, Alexander Jussupow, Evgeny Kirilin, Alessandro Laio, Vittorio Limongelli, Kresten Lindorff-Larsen, Thomas Löhr, Fabrizio Marinelli, Layla Martin-Samos, Matteo Masetti, Ralf Meyer, Angelos Michaelides, Carla Molteni, Tetsuya Morishita, Marco Nava, Cristina Paissoni, Elena Papaleo, Michele Parrinello, Jim Pfaendtner, Pablo Piaggi, GiovanniMaria Piccini, Adriana Pietropaolo, Fabio Pietrucci, Silvio Pipolo, Davide Provasi, David Quigley, Paolo Raiteri, Stefano Raniolo, Jakub Rydzewski, Matteo Salvalaglio, Gabriele Cesare Sosso, Vojtěch Spiwok, Jiří Šponer, David W. H. Swenson, Pratyush Tiwary, Omar Valsson, Michele Vendruscolo, Gregory A. Voth & Andrew White
المصدر: Nature Methods
Nature Methods, 2019, 16 (8), pp.670-673. ⟨10.1038/s41592-019-0506-8⟩
The PLUMED consortium 2019, ' Promoting transparency and reproducibility in enhanced molecular simulations ', Nature Methods, vol. 16, no. 8, pp. 670-673 . https://doi.org/10.1038/s41592-019-0506-8
Nature methods 16(8), 670-673 (2019). doi:10.1038/s41592-019-0506-8
Nature Methods, Nature Publishing Group, 2019, 16 (8), pp.670-673. ⟨10.1038/s41592-019-0506-8⟩
Bonomi, M, Bussi, G, Camilloni, C, Tribello, G A, Banas, P, Barducci, A, Bernetti, M, Bolhuis, P G, Bottaro, S, Branduardi, D, Capelli, R, Carloni, P, Ceriotti, M, Cesari, A, Chen, H, Chen, W, Colizzi, F, De, S, De La Pierre, M, Donadio, D, Drobot, V, Ensing, B, Ferguson, A L, Filizola, M, Fraser, J S, Fu, H, Gasparotto, P, Gervasio, F L, Giberti, F, Gil-Ley, A, Giorgino, T, Heller, G T, Hocky, G M, Iannuzzi, M, Invernizzi, M, Jelfs, K E, Jussupow, A, Kirilin, E, Laio, A, Limongelli, V, Lindorff-Larsen, K, Lohr, T, Marinelli, F, Martin-Samos, L, Masetti, M, Meyer, R, Michaelides, A, Molteni, C, Morishita, T, Nava, M, Paissoni, C, Papaleo, E, Parrinello, M, Pfaendtner, J, Piaggi, P, Piccini, G, Pietropaolo, A, Pietrucci, F, Pipolo, S, Provasi, D, Quigley, D, Raiteri, P, Raniolo, S, Rydzewski, J, Salvalaglio, M, Sosso, G C, Spiwok, V, Sponer, J, Swenson, D W H, Tiwary, P, Valsson, O, Vendruscolo, M, Voth, G A & White, A 2019, ' Promoting transparency and reproducibility in enhanced molecular simulations ', Nature Methods, vol. 16, no. 8, pp. 670-673 . https://doi.org/10.1038/s41592-019-0506-8
Nature Methods, 16(8), 670-673. Nature Publishing Group
Nature methods (Online) 16 (2019): 670. doi:10.1038/s41592-019-0506-8
info:cnr-pdr/source/autori:Massimiliano Bonomi, Giovanni Bussi, Carlo Camilloni, Gareth A. Tribello, Pavel Baná?, Alessandro Barducci, Mattia Bernetti, Peter G. Bolhuis, Sandro Bottaro, Davide Branduardi, Riccardo Capelli, Paolo Carloni, Michele Ceriotti, Andrea Cesari, Haochuan Chen, Wei Chen, Francesco Colizzi, Sandip De, Marco De La Pierre, Davide Donadio, Viktor Drobot, Bernd Ensing, Andrew L. Ferguson, Marta Filizola, James S. Fraser, Haohao Fu, Piero Gasparotto, Francesco Luigi Gervasio, Federico Giberti, Alejandro Gil-Ley, Toni Giorgino, Gabriella T. Heller, Glen M. Hocky, Marcella Iannuzzi, Michele Invernizzi, Kim E. Jelfs, Alexander Jussupow, Evgeny Kirilin, Alessandro Laio, Vittorio Limongelli, Kresten Lindorff-Larsen, Thomas Löhr, Fabrizio Marinelli, Layla Martin-Samos, Matteo Masetti, Ralf Meyer, Angelos Michaelides, Carla Molteni, Tetsuya Morishita, Marco Nava, Cristina Paissoni, Elena Papaleo, Michele Parrinello, Jim Pfaendtner, Pablo Piaggi, GiovanniMaria Piccini, Adriana Pietropaolo, Fabio Pietrucci, Silvio Pipolo, Davide Provasi, David Quigley, Paolo Raiteri, Stefano Raniolo, Jakub Rydzewski, Matteo Salvalaglio, Gabriele Cesare Sosso, Vojt?ch Spiwok, Ji?í ?poner, David W. H. Swenson, Pratyush Tiwary, Omar Valsson, Michele Vendruscolo, Gregory A. Voth, Andrew White/titolo:Promoting transparency and reproducibility in enhanced molecular simulations/doi:10.1038%2Fs41592-019-0506-8/rivista:Nature methods (Online)/anno:2019/pagina_da:670/pagina_a:/intervallo_pagine:670/volume:16مصطلحات موضوعية: Models, Molecular, DYNAMICS, enhanced-sampling, free-energy calculations, molecular dynamics simulations, transparency, reproducibility, dissemination, Biochemistry & Molecular Biology, Computer science, Molecular Conformation, Molecular Dynamics Simulation, Biochemistry, Biochemical Research Methods, Settore FIS/03 - Fisica della Materia, 03 medical and health sciences, 10 Technology, Humans, ddc:610, reproducibility, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 11 Medical and Health Sciences, 030304 developmental biology, 0303 health sciences, Reproducibility, Science & Technology, PLUMED consortium, Reproducibility of Results, Cell Biology, 06 Biological Sciences, simulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Transparency (graphic), Systems engineering, Life Sciences & Biomedicine, Software, Biotechnology, Developmental Biology
الوصف: The PLUMED consortium unifies developers and contributors to PLUMED, an open-source library for enhanced-sampling, free-energy calculations and the analysis of molecular dynamics simulations. Here, we outline our efforts to promote transparency and reproducibility by disseminating protocols for enhanced-sampling molecular simulations.
وصف الملف: application/pdf; ELETTRONICO
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المصدر: Methods in molecular biology (Clifton, N.J.). 2022
مصطلحات موضوعية: Models, Molecular, Protein Conformation, Bayes Theorem, Molecular Dynamics Simulation, Peptides, Nuclear Magnetic Resonance, Biomolecular, Algorithms
الوصف: Accurate protein structural ensembles can be determined with metainference, a Bayesian inference method that integrates experimental information with prior knowledge of the system and deals with all sources of uncertainty and errors as well as with system heterogeneity. Furthermore, metainference can be implemented using the metadynamics approach, which enables the computational study of complex biological systems requiring extensive conformational sampling. In this chapter, we provide a step-by-step guide to perform and analyse metadynamic metainference simulations using the ISDB module of the open-source PLUMED library, as well as a series of practical tips to avoid common mistakes. Specifically, we will guide the reader in the process of learning how to model the structural ensemble of a small disordered peptide by combining state-of-the-art molecular mechanics force fields with nuclear magnetic resonance data, including chemical shifts, scalar couplings and residual dipolar couplings.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=pmid________::e86134f4ec1476acba932110a78e9422
https://pubmed.ncbi.nlm.nih.gov/31396909 -
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المؤلفون: Michele Vendruscolo, Carlo Camilloni, Samuel Reghim Silva, Rinaldo W. Montalvao, Antonio Marinho da Silva Neto
المصدر: Proteins: Structure, Function, and Bioinformatics.
مصطلحات موضوعية: Models, Molecular, Protein Conformation, Curvature, Biochemistry, Proto-Oncogene Proteins c-myb, 03 medical and health sciences, Superposition principle, Software, Structural Biology, Animals, Cluster Analysis, Humans, Statistical physics, Cluster analysis, Molecular Biology, Conformational ensembles, 030304 developmental biology, Mathematics, Principal Component Analysis, 0303 health sciences, Ubiquitin, business.industry, 030302 biochemistry & molecular biology, Proteins, Metric space, Differential geometry, Torsion (algebra), business
الوصف: Here a differential geometry (DG) representation of protein backbone is explored on the analyses of protein conformational ensembles. The protein backbone is described by curvature, κ, and torsion, τ, values per residue and we propose 1) a new dissimilarity and protein flexibility measurement and 2) a local conformational clustering method. The methods were applied to Ubiquitin and c-Myb-KIX protein conformational ensembles and results show that κ\τ metric space allows to properly judge protein flexibility by avoiding the superposition problem. The dmax measurement presents equally good or superior results when compared to RMSF, especially for the intrinsically unstructured protein. The clustering method is unique as it relates protein global to local dynamics by providing a global clustering solutions per residue. The methods proposed can be especially useful to the analyses of highly flexible proteins. The software written for the analyses presented here is available at https://github.com/AMarinhoSN/FleXgeo for academic usage only.
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المؤلفون: Eva Schad, Silvio C. E. Tosatto, Alexander Miguel Monzon, Zsuzsanna Dosztányi, Ivan Mičetić, Damiano Piovesan, Pietro Sormanni, Lisanna Paladin, Francesco Tabaro, Bálint Mészáros, Gustavo Parisi, Michele Vendruscolo, Carlo Camilloni, Peter Tompa, Marco Necci, Wim F. Vranken, Norman E. Davey
المساهمون: Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, University of Tampere, Structural Biology Brussels, Department of Bio-engineering Sciences, Informatics and Applied Informatics, Chemistry, Basic (bio-) Medical Sciences
المصدر: Nucleic acids research, 46 (D1
Nucleic Acids Research
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICETمصطلحات موضوعية: Models, Molecular, 0301 basic medicine, Protein Folding, DATABASE, Protein Data Bank (RCSB PDB), Datasets as Topic, Information layer, Roentgen rays, Computational biology, Biology, Indirect evidence, Biokemia, solu- ja molekyylibiologia - Biochemistry, cell and molecular biology, purl.org/becyt/ford/1 [https], 03 medical and health sciences, Annotation, Journal Article, Genetics, Database Issue, Humans, Protein Interaction Domains and Motifs, Amino Acid Sequence, Databases, Protein, Protein secondary structure, Search function, Internet, Binding Sites, PROTEIN DISORDER, Molecular Sequence Annotation, purl.org/becyt/ford/1.2 [https], Intrinsically Disordered Proteins, Gene Ontology, 030104 developmental biology, Ciencias de la Computación e Información, INTRINSIC DISORDER, UniProt, Sequence Alignment, Biologie, Ciencias de la Información y Bioinformática, Software, CIENCIAS NATURALES Y EXACTAS, Protein Binding
الوصف: The MobiDB (URL: mobidb.bio.unipd.it) database of protein disorder and mobility annotations has been significantly updated and upgraded since its last major renewal in 2014. Several curated datasets for intrinsic disorder and folding upon binding have been integrated from specialized databases. The indirect evidence has also been expanded to better capture information available in the PDB, such as high temperature residues in X-ray structures and overall conformational diversity. Novel nuclear magnetic resonance chemical shift data provides an additional experimental information layer on conformational dynamics. Predictions have been expanded to provide new types of annotation on backbone rigidity, secondary structure preference and disordered binding regions. MobiDB 3.0 contains information for the complete UniProt protein set and synchronization has been improved by covering all UniParc sequences. An advanced search function allows the creation of a wide array of custom-made datasets for download and further analysis. A large amount of information and cross-links to more specialized databases are intended to make MobiDB the central resource for the scientific community working on protein intrinsic disorder and mobility.
SCOPUS: ar.j
info:eu-repo/semantics/publishedوصف الملف: application/pdf; fulltext; D471-D476; 1 full-text file(s): application/pdf
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2a173b8e499eafa1f22f66340d235ae
https://academic.oup.com/nar/article/46/D1/D471/4612964 -
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المؤلفون: Johannes Buchner, Manuel Hora, Carlo Camilloni, Pamina Kazman, Christoph Göbl, Bernd Reif, Benedikt Weber
المصدر: J. Mol. Biol. 430, 4925-4940 (2018)
مصطلحات موضوعية: Models, Molecular, 0301 basic medicine, Amyloid, Protein Conformation, Proteolysis, Arginine, Immunoglobulin light chain, Fibril, Antibody Folding, Protein Stability, Light Chain Linker, Intramolecular Interactions, Protein Aggregation, Pathological, 03 medical and health sciences, Residue (chemistry), Amyloid disease, Protein Domains, Structural Biology, medicine, Humans, Nuclear Magnetic Resonance, Biomolecular, Molecular Biology, Binding Sites, 030102 biochemistry & molecular biology, medicine.diagnostic_test, Chemistry, 030104 developmental biology, Residual dipolar coupling, Mutation, Biophysics, Immunoglobulin Light Chains, Linker
الوصف: The antibody light chain (LC) consists of two domains and is essential for antigen binding in mature immunoglobulins. The two domains are connected by a highly conserved linker that comprises the structurally important Arg108 residue. In antibody light chain (AL) amyloidosis, a severe protein amyloid disease, the LC and its N-terminal variable domain (V-L) convert to fibrils deposited in the tissues causing organ failure. Understanding the factors shaping the architecture of the LC is important for basic science, biotechnology and for deciphering the principles that lead to fibril formation. In this study, we examined the structure and properties of LC variants with a mutated or extended linker. We show that under destabilizing conditions, the linker modulates the amyloidogenicity of the LC. The fibril formation propensity of LC linker variants and their susceptibility to proteolysis directly correlate implying an interplay between the two LC domains. Using NMR and residual dipolar coupling-based simulations, we found that the linker residue Arg108 is a key factor regulating the relative orientation of the VL and CL domains, keeping them in a bent and dense, but still flexible conformation. Thus, inter-domain contacts and the relative orientation of VL and CL to each other are of major importance for maintaining the structural integrity of the full-length LC. (C) 2018 Elsevier Ltd. All rights reserved.
وصف الملف: application/pdf
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f8a266856d366d146ff587a41c6b5124
https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=54713 -
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المؤلفون: Carlo Camilloni, Massimiliano Bonomi
المساهمون: Università degli Studi di Milano [Milano] (UNIMI)
المصدر: Bioinformatics
Bioinformatics, Oxford University Press (OUP), 2017, 33 (24), pp.3999-4000. ⟨10.1093/bioinformatics/btx529⟩مصطلحات موضوعية: 0301 basic medicine, Statistics and Probability, Models, Molecular, Molecular Conformation, Computational biology, 010402 general chemistry, 01 natural sciences, Biochemistry, 03 medical and health sciences, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Structure (mathematical logic), Supplementary data, Experimental data, Bayes Theorem, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], ISDB, 0104 chemical sciences, Computer Science Applications, Variety (cybernetics), Computational Mathematics, 030104 developmental biology, Computational Theory and Mathematics, A priori and a posteriori, Bayesian framework, Noise (video), Biological system, Software
الوصف: Summary Accurate structural models of biological systems can be obtained by properly combining experimental data with a priori physico–chemical knowledge. Here we present PLUMED-ISDB, an open-source, freely-available module of the popular PLUMED library, which enables the simultaneous determination of structure and dynamics of conformationally heterogeneous systems by integrating experimental data with a priori information. This integration is achieved using metainference, a general Bayesian framework that accounts for both noise in the data and their ensemble-averaged nature. PLUMED-ISDB implements different types of experimental data, such as several NMR observables, FRET, SAXS and cryo-electron microscopy data, and enables modelling structure and dynamics of individual proteins, protein complexes, membrane proteins, RNA and DNA, using a variety of enhanced sampling methods and resolutions of the system. Availability and implementation PLUMED-ISDB is freely available at www.plumed.org. Supplementary information Supplementary data are available at Bioinformatics online.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2e2a883e7a9581e7d4e4a57b950cd47
https://hal.archives-ouvertes.fr/hal-03136441 -
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المساهمون: University of Cambridge [UK] (CAM), Università degli Studi di Milano [Milano] (UNIMI), Bonomi, Massimilano [0000-0002-7321-0004], Heller, Gabrielle [0000-0002-5672-0467], Vendruscolo, Michele [0000-0002-3616-1610], Apollo - University of Cambridge Repository
المصدر: Current Opinion in Structural Biology
Current Opinion in Structural Biology, Elsevier, 2017, 42, pp.106-116. ⟨10.1016/j.sbi.2016.12.004⟩مصطلحات موضوعية: 0301 basic medicine, Models, Molecular, 010304 chemical physics, Protein molecules, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Entropy, Proteins, Nanotechnology, Computational biology, 01 natural sciences, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Visualization, 03 medical and health sciences, 030104 developmental biology, Protein structure, Structural Biology, 0103 physical sciences, Human proteome project, Humans, Molecular Biology
الوصف: International audience; The biological functions of protein molecules are intimately contingent on their conformational dynamics. This aspect is particularly evident for disordered proteins, which constitute about one-third of the human proteome. Therefore, structural ensembles often offer more useful representations of proteins than individual conformations. Here, we describe how the well-established principles of protein structure determination should be extended to the case of protein structural ensembles determination. These principles concern primarily how to deal with conformationally heterogeneous states, and with experimental measurements that are averaged over such states and affected by a variety of errors. We first review the vast literature of recent methods that combine experimental and computational information to model structural ensembles, highlighting their similarities and differences. We then address some conceptual problems in the determination of structural ensembles and define future goals towards the establishment of objective criteria for the comparison, validation, visualization, and dissemination of such ensembles.
وصف الملف: application/pdf
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