13 results on '"Radusky, Leandro G."'
Search Results
2. Frustraevo: a web server to localize and quantify the conservation of local energetic frustration in protein families.
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Parra, R Gonzalo, Freiberger, Maria I, Poley-Gil, Miriam, Fernandez-Martin, Miguel, Radusky, Leandro G, Ruiz-Serra, Victoria, Wolynes, Peter G, Ferreiro, Diego U, and Valencia, Alfonso
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- 2024
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3. Protein-assisted RNA fragment docking (RnaX) for modeling RNA–protein interactions using ModelX
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Blanco, Javier Delgado, Radusky, Leandro G., Cianferoni, Damiano, and Serrano, Luis
- Published
- 2019
4. pyFoldX: enabling biomolecular analysis and engineering along structural ensembles.
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Radusky, Leandro G and Serrano, Luis
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STRUCTURAL analysis (Engineering) , *PYTHON programming language , *PROTEIN engineering , *INTERNET servers , *PROTEIN structure , *DESIGN software , *SOFTWARE architecture - Abstract
Summary Recent years have seen an increase in the number of structures available, not only for new proteins but also for the same protein crystallized with different molecules and proteins. While protein design software has proven to be successful in designing and modifying proteins, they can also be overly sensitive to small conformational differences between structures of the same protein. To cope with this, we introduce here pyFoldX, a python library that allows the integrative analysis of structures of the same protein using FoldX, an established forcefield and modelling software. The library offers new functionalities for handling different structures of the same protein, an improved molecular parametrization module and an easy integration with the data analysis ecosystem of the python programming language. Availability and implementation pyFoldX rely on the FoldX software for energy calculations and modelling, which can be downloaded upon registration in http://foldxsuite.crg.eu/ and its licence is free of charge for academics. The pyFoldX library is open-source. Full details on installation, tutorials covering the library functionality and the scripts used to generate the data and figures presented in this paper are available at https://github.com/leandroradusky/pyFoldX. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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5. Protein-assisted RNA fragment docking (RnaX) for modeling RNA–protein interactions using ModelX.
- Author
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Delgado Blanco, Javier, Radusky, Leandro G., Cianferoni, Damiano, and Serrano, Luis
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RNA-protein interactions , *RNA , *PROTEIN engineering , *GENE silencing , *PHYSIOLOGICAL control systems - Abstract
RNA–protein interactions are crucial for such key biological processes as regulation of transcription, splicing, translation, and gene silencing, among many others. Knowing where an RNA molecule interacts with a target protein and/or engineering an RNA molecule to specifically bind to a protein could allow for rational interference with these cellular processes and the design of novel therapies. Here we present a robust RNA–protein fragment pairbased method, termed RnaX, to predict RNA-binding sites. This methodology, which is integrated into the ModelX tool suite (http://modelx.crg.es), takes advantage of the structural information present in all released RNA–protein complexes. This information is used to create an exhaustive database for docking and a statistical forcefield for fast discrimination of true backbone-compatible interactions. RnaX, together with the protein design forcefield FoldX, enables us to predict RNA–protein interfaces and, when sufficient crystallographic information is available, to reengineer the interface at the sequence-specificity level by mimicking those conformational changes that occur on protein and RNA mutagenesis. These results, obtained at just a fraction of the computational cost of methods that simulate conformational dynamics, open up perspectives for the engineering of RNA–protein interfaces. [ABSTRACT FROM AUTHOR]
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- 2019
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6. FrustratometeR: an R-package to compute local frustration in protein structures, point mutants and MD simulations.
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Rausch, Atilio O, Freiberger, Maria I, Leonetti, Cesar O, Luna, Diego M, Radusky, Leandro G, Wolynes, Peter G, Ferreiro, Diego U, and Parra, R Gonzalo
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PROTEIN structure ,FRUSTRATION ,COMPUTER workstation clusters ,PROTEIN analysis ,MOLECULAR dynamics - Abstract
Summary Once folded, natural protein molecules have few energetic conflicts within their polypeptide chains. Many protein structures do however contain regions where energetic conflicts remain after folding, i.e. they are highly frustrated. These regions, kept in place over evolutionary and physiological timescales, are related to several functional aspects of natural proteins such as protein–protein interactions, small ligand recognition, catalytic sites and allostery. Here, we present FrustratometeR, an R package that easily computes local energetic frustration on a personal computer or a cluster. This package facilitates large scale analysis of local frustration, point mutants and molecular dynamics (MD) trajectories, allowing straightforward integration of local frustration analysis into pipelines for protein structural analysis. Availability and implementation https://github.com/proteinphysiologylab/frustratometeR. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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7. ProteinFishing: a protein complex generator within the ModelX toolsuite.
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Cianferoni, Damiano, Radusky, Leandro G, Head, Sarah A, Serrano, Luis, and Delgado, Javier
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INTERNET servers , *RELATIONAL databases , *ALGORITHMS , *PROTEIN-protein interactions , *PROTEINS , *STRUCTURAL models - Abstract
Summary Accurate 3D modelling of protein–protein interactions (PPI) is essential to compensate for the absence of experimentally determined complex structures. Here, we present a new set of commands within the ModelX toolsuite capable of generating atomic-level protein complexes suitable for interface design. Among these commands, the new tool ProteinFishing proposes known and/or putative alternative 3D PPI for a given protein complex. The algorithm exploits backbone compatibility of protein fragments to generate mutually exclusive protein interfaces that are quickly evaluated with a knowledge-based statistical force field. Using interleukin-10-R2 co-crystalized with interferon-lambda-3, and a database of X-ray structures containing interleukin-10, this algorithm was able to generate interleukin-10-R2/interleukin-10 structural models in agreement with experimental data. Availability and implementation ProteinFishing is a portable command-line tool included in the ModelX toolsuite, written in C++, that makes use of an SQL (tested for MySQL and MariaDB) relational database delivered with a template SQL dump called FishXDB. FishXDB contains the empty tables of ModelX fragments and the data used by the embedded statistical force field. ProteinFishing is compiled for Linux-64bit, MacOS-64bit and Windows-32bit operating systems. This software is a proprietary license and is distributed as an executable with its correspondent database dumps. It can be downloaded publicly at http://modelx.crg.es/. Licenses are freely available for academic users after registration on the website and are available under commercial license for for-profit organizations or companies. Contact javier.delgado@crg.eu or luis.serrano@crg.eu Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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8. The Druggable Pocketome of Corynebacterium diphtheriae: A New Approach for in silico Putative Druggable Targets.
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Hassan, Syed S., Jamal, Syed B., Radusky, Leandro G., Tiwari, Sandeep, Ullah, Asad, Ali, Javed, Behramand, de Carvalho, Paulo V. S. D., Shams, Rida, Khan, Sabir, Figueiredo, Henrique C. P., Barh, Debmalya, Ghosh, Preetam, Silva, Artur, Baumbach, Jan, Röttger, Richard, Turjanski, Adrián G., and Azevedo, Vasco A. C.
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CORYNEBACTERIUM diphtheriae ,PHARMACOGENOMICS ,TARGETED drug delivery - Abstract
Diphtheria is an acute and highly infectious disease, previously regarded as endemic in nature but vaccine-preventable, is caused by Corynebacterium diphtheriae (Cd). In this work, we used an in silico approach along the 13 complete genome sequences of C. diphtheriae followed by a computational assessment of structural information of the binding sites to characterize the "pocketome druggability." To this end, we first computed the "modelome" (3D structures of a complete genome) of a randomly selected reference strain Cd NCTC13129; that had 13,763 open reading frames (ORFs) and resulted in 1,253 (9%) structure models. The amino acid sequences of these modeled structures were compared with the remaining 12 genomes and consequently, 438 conserved protein sequences were obtained. The RCSB-PDB database was consulted to check the template structures for these conserved proteins and as a result, 401 adequate 3D models were obtained. We subsequently predicted the protein pockets for the obtained set of models and kept only the conserved pockets that had highly druggable (HD) values (137 across all strains). Later, an off-target host homology analyses was performed considering the human proteome using NCBI database. Furthermore, the gene essentiality analysis was carried out that gave a final set of 10-conserved targets possessing highly druggable protein pockets. To check the target identification robustness of the pipeline used in this work, we crosschecked the final target list with another in-house target identification approach for C. diphtheriae thereby obtaining three common targets, these were; hisE-phosphoribosyl-ATP pyrophosphatase, glpX-fructose 1,6-bisphosphatase II, and rpsH-30S ribosomal protein S8. Our predicted results suggest that the in silico approach used could potentially aid in experimental polypharmacological target determination in C. diphtheriae and other pathogens, thereby, might complement the existing and new drug-discovery pipelines. [ABSTRACT FROM AUTHOR]
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- 2018
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9. Protein Frustratometer 2: a tool to localize energetic frustration in protein molecules, now with electrostatics.
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Parra, R. Gonzalo, Schafer, Nicholas P., Radusky, Leandro G., Min-Yeh Tsai, Guzovsky, A. Brenda, Wolynes, Peter G., and Ferreiro, Diego U.
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- 2016
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10. An integrated structural proteomics approach along the druggable genome of Corynebacterium pseudotuberculosis species for putative druggable targets.
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Radusky, Leandro G., Hassan, Syed Shah, Lanzarotti, Esteban, Tiwari, Sandeep, Jamal, Syed Babar, Ali, Javed, Ali, Amjad, Ferreira, Rafaela Salgado, Barh, Debmalya, Silva, Artur, Turjanski, Adrián G., and Azevedo, Vasco A. C.
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STRUCTURAL proteomics , *CORYNEBACTERIUM pseudotuberculosis , *MICROBIAL virulence , *DRUG development , *HOMOLOGY (Biochemistry) - Abstract
Background: The bacterium Corynebacterium pseudotuberculosis (Cp) causes caseous lymphadenitis (CLA), mastitis, ulcerative lymphangitis, and oedema in a number of hosts, comprising ruminants, thereby intimidating economic and dairy industries worldwide. So far there is no effective drug or vaccine available against Cp. Previously, a pan-genomic analysis was performed for both biovar equi and biovar ovis and a Pathogenicity Islands (PAIS) analysis within the strains highlighted a large set of proteins that could be relevant therapeutic targets for controlling the onset of CLA. In the present work, a structural druggability analysis pipeline was accomplished along 15 previously sequenced Cp strains from both biovar equi and biovar ovis. Methods and results: We computed the whole modelome of a reference strain Cp1002 (NCBI Accession: NC_017300.1) and then the homology models of proteins, of 14 different Cp strains, with high identity (≥ 85%) to the reference strain were also done. Druggability score of all proteins pockets was calculated and only those targets that have a highly druggable (HD) pocket in all strains were kept, a set of 58 proteins. Finally, this information was merged with the previous PAIS analysis giving two possible highly relevant targets to conduct drug discovery projects. Also, off-targeting information against host organisms, including Homo sapiens and a further analysis for protein essentiality provided a final set of 31 druggable, essential and non-host homologous targets, tabulated in table S4, additional file 1. Out of 31 globally druggable targets, 9 targets have already been reported in other pathogenic microorganisms, 3 of them (3-isopropylmalate dehydratase small subunit, 50S ribosomal protein L30, Chromosomal replication initiator protein DnaA) in C. pseudotuberculosis. Conclusion: Overall we provide valuable information of possible targets against C. pseudotuberculosis where some of these targets have already been reported in other microorganisms for drug discovery projects, also discarding targets that might be physiologically relevant but are not amenable for drug binding. We propose that the [ABSTRACT FROM AUTHOR]
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- 2015
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11. Protein frustratometer: a tool to localize energetic frustration in protein molecules.
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Jenik, Michael, Parra, R. Gonzalo, Radusky, Leandro G., Turjanski, Adrian, Wolynes, Peter G., and Ferreiro, Diego U.
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- 2012
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12. FoldX 5.0: working with RNA, small molecules and a new graphical interface.
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Delgado, Javier, Radusky, Leandro G, Cianferoni, Damiano, and Serrano, Luis
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SMALL molecules , *GRAPHICAL user interfaces , *RNA - Abstract
Summary A new version of FoldX, whose main new features allows running classic FoldX commands on structures containing RNA molecules and includes a module that allows parametrization of ligands or small molecules (ParamX) that were not previously recognized in old versions, has been released. An extended FoldX graphical user interface has also being developed (available as a python plugin for the YASARA molecular viewer) allowing user-friendly parametrization of new custom user molecules encoded using JSON format. Availability and implementation http://foldxsuite.crg.eu/ [ABSTRACT FROM AUTHOR]
- Published
- 2019
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13. Wnt binding to Coatomer proteins directs secretion on exosomes independently of palmitoylation.
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Gurriaran-Rodriguez U, Datzkiw D, Radusky LG, Esper M, Xiao F, Ming H, Fisher S, Rojas MA, De Repentigny Y, Kothary R, Rojas AL, Serrano L, Hierro A, and Rudnicki MA
- Abstract
Wnt proteins are secreted hydrophobic glycoproteins that act over long distances through poorly understood mechanisms. We discovered that Wnt7a is secreted on extracellular vesicles (EVs) following muscle injury. Structural analysis identified the motif responsible for Wnt7a secretion on EVs that we term the Exosome Binding Peptide (EBP). Addition of the EBP to an unrelated protein directed secretion on EVs. Disruption of palmitoylation, knockdown of WLS, or deletion of the N-terminal signal peptide did not affect Wnt7a secretion on purified EVs. Bio-ID analysis identified Coatomer proteins as candidates responsible for loading Wnt7a onto EVs. The crystal structure of EBP bound to the COPB2 coatomer subunit, the binding thermodynamics, and mutagenesis experiments, together demonstrate that a dilysine motif in the EBP mediates binding to COPB2. Other Wnts contain functionally analogous structural motifs. Mutation of the EBP results in a significant impairment in the ability of Wnt7a to stimulate regeneration, indicating that secretion of Wnt7a on exosomes is critical for normal regeneration in vivo . Our studies have defined the structural mechanism that mediates binding of Wnt7a to exosomes and elucidated the singularity of long-range Wnt signalling.
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- 2023
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