Estudis computacionals sobre beta-amilasa, una molècula enzimàtica tipus barril (beta/alfa) 8: relacions evolutives i transicions estructurals al centre catalític..

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SRide: a server for identifying stabilizing residues in proteins

Residues expected to play key roles in the stabilization of proteins [stabilizing residues (SRs)] are selected by combining several methods based mainly on the interactions of a given residue with its spatial, rather than its sequential neighborhood and by considering the evolutionary conservation of the residues. A residue is selected as a stabilizing residue if it has high surrounding hydrophobicity, high long-range order, high conservation score and if it belongs to a stabilization center. The definition of all these parameters and the thresholds used to identify the SRs are discussed in detail. The algorithm for identifying SRs was originally developed for TIM-barrel proteins [M. M. Gromiha, G. Pujadas, C. Magyar, S. Selvaraj, and I. Simon (2004), Proteins, 55, 316–329] and is now generalized for all proteins of known 3D structure. SRs could be applied in protein engineering and homology modeling and could also help to explain certain folds with significant stability. The SRide server is located at

Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases

Altres ajuts: Generalitat de Catalunya, Departament de Salut; Generalitat de Catalunya, Departament d'Empresa i Coneixement i CERCA Program; Ministerio de Ciencia e Innovación; Instituto Nacional de Bioinformática; ELIXIR Implementation Studies (CNAG-CRG); Centro de Investigaciones Biomédicas en Red de Enfermedades Raras; Centro de Excelencia Severo Ochoa; European Regional Development Fund (FEDER).Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7%), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%)

Identification of Human IKK-2 Inhibitors of Natural Origin (Part I): Modeling of the IKK-2 Kinase Domain, Virtual Screening and Activity Assays

BACKGROUND: Their large scaffold diversity and properties, such as structural complexity and drug similarity, form the basis of claims that natural products are ideal starting points for drug design and development. Consequently, there has been great interest in determining whether such molecules show biological activity toward protein targets of pharmacological relevance. One target of particular interest is hIKK-2, a serine-threonine protein kinase belonging to the IKK complex that is the primary component responsible for activating NF-κB in response to various inflammatory stimuli. Indeed, this has led to the development of synthetic ATP-competitive inhibitors for hIKK-2. Therefore, the main goals of this study were (a) to use virtual screening to identify potential hIKK-2 inhibitors of natural origin that compete with ATP and (b) to evaluate the reliability of our virtual-screening protocol by experimentally testing the in vitro activity of selected natural-product hits. METHODOLOGY/PRINCIPAL FINDINGS: We thus predicted that 1,061 out of the 89,425 natural products present in the studied database would inhibit hIKK-2 with good ADMET properties. Notably, when these 1,061 molecules were merged with the 98 synthetic hIKK-2 inhibitors used in this study and the resulting set was classified into ten clusters according to chemical similarity, there were three clusters that contained only natural products. Five molecules from these three clusters (for which no anti-inflammatory activity has been previously described) were then selected for in vitro activity testing, in which three out of the five molecules were shown to inhibit hIKK-2. CONCLUSIONS/SIGNIFICANCE: We demonstrated that our virtual-screening protocol was successful in identifying lead compounds for developing new inhibitors for hIKK-2, a target of great interest in medicinal chemistry. Additionally, all the tools developed during the current study (i.e., the homology model for the hIKK-2 kinase domain and the pharmacophore) will be made available to interested readers upon request

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Disseny i prototipat d'un sistema basat en rodaments magnètics

L’objectiu que segueix aquest projecte és dissenyar i, posteriorment, prototipar un sistema de levitació magnètica basat en rodaments magnètics radials. Per assolir-lo s’estudia l’estat de la tecnologia per aprofundir en els principis físics que regeixen la suspensió magnètica, les limitacions que presenta l’estat actual de la tecnologia i quins avantatges presenten els rodaments magnètics respecte als rodaments clàssics. Aquest sistema es basa en un control PID d’un rodament magnètic. Per aconseguir implementar aquest PID són primordials tres elements: l’actuador, els sensors i el controlador. Pel que fa a l’actuador s’utilitza un estator d’un motor pas a pas. Els sensors són dues videocàmeres, i el controlador és una Raspberry Pi, la qual es programa utilitzant el programa Matlab, que ens aporta una facilitat extra a l’hora d’implementar el control PID, i de fer una visualització, en temps real, de l’estat de les variables. La finalitat d’aquest disseny és implementar l’estudi fet en la creació d’un reòmetre sense contacte que, reduint les pèrdues per fricció, aporti un augment en la sensibilitat del sensor

Disseny i prototipat d'un sistema basat en rodaments magnètics

L’objectiu que segueix aquest projecte és dissenyar i, posteriorment, prototipar un sistema de levitació magnètica basat en rodaments magnètics radials. Per assolir-lo s’estudia l’estat de la tecnologia per aprofundir en els principis físics que regeixen la suspensió magnètica, les limitacions que presenta l’estat actual de la tecnologia i quins avantatges presenten els rodaments magnètics respecte als rodaments clàssics. Aquest sistema es basa en un control PID d’un rodament magnètic. Per aconseguir implementar aquest PID són primordials tres elements: l’actuador, els sensors i el controlador. Pel que fa a l’actuador s’utilitza un estator d’un motor pas a pas. Els sensors són dues videocàmeres, i el controlador és una Raspberry Pi, la qual es programa utilitzant el programa Matlab, que ens aporta una facilitat extra a l’hora d’implementar el control PID, i de fer una visualització, en temps real, de l’estat de les variables. La finalitat d’aquest disseny és implementar l’estudi fet en la creació d’un reòmetre sense contacte que, reduint les pèrdues per fricció, aporti un augment en la sensibilitat del sensor