Institut de Recerca Biomèdica (IRB Barcelona): Envíos recientes
Mostrando ítems 41-60 de 418
Challenges of docking in large, flexible and promiscuous binding sites
After decades of work, the correct determination of the binding mode of a small molecule into a target protein is still a challenging problem, whose difficulty depends on: i) the sizes of the binding site and the ligand; ...
BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis
Circadian rhythms control organismal physiology throughout the day. At the cellular level, clock regulation is established by a self-sustained Bmal1-dependent transcriptional oscillator network. However, it is still unclear ...
The multiple roles of waters in protein solvation
Extensive molecular dynamics (MD) simulations have been used to characterize the multiple roles of water in solvating different types of proteins under different environmental conditions. We analyzed a small set of proteins, ...
Proteomic tools for the quantitative analysis of artificial peptide libraries: detection and characterization of target-amplified PD-1 inhibitors
We report a quantitative proteomics data analysis pipeline which, coupled to protein-directed dynamic combinatorial chemistry (DDC) experiments, enables the rapid discovery and direct characterization of protein-protein ...
A single-cell resolved genotype-phenotype map using genome-wide genetic and environmental perturbations
Heterogeneity is inherent to living organisms and it determines cell fate and phenotypic variability. Despite its ubiquity, the underlying molecular mechanisms and the genetic basis linking genotype to-phenotype heterogeneity ...
BioSuper: A web tool for the superimposition of biomolecules and assemblies with rotational symmetry
Background Most of the proteins in the Protein Data Bank (PDB) are oligomeric complexes consisting of two or more subunits that associate by rotational or helical symmetries. Despite the myriad of superimposition tools in ...
Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming
The expression of the pluripotency factors OCT4, SOX2, KLF4, and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, partial and reversible reprogramming ...
Detecting similar binding pockets to enable systems polypharmacology
In the era of systems biology, multi-target pharmacological strategies hold promise for tackling disease-related networks. In this regard, drug promiscuity may be leveraged to interfere with multiple receptors: the so-called ...
Chasing molecular glue degraders: screening approaches
Protein-protein interactions (PPIs) govern all biological processes. Some small molecules modulate PPIs through induced protein proximity. In particular, molecular glue degraders are monovalent compounds that orchestrate ...
Pre-exascale HPC approaches for molecular dynamics simulations. Covid-19 research: A use case
Exascale computing has been a dream for ages and is close to becoming a reality that will impact how molecular simulations are being performed, as well as the quantity and quality of the information derived for them. We ...
Centrosome Amplification Increases Single-Cell Branching in Post-mitotic Cells
Centrosome amplification is a hallmark of cancer, although we are still far from understanding how this process affects tumorigenesis [1, 2]. Besides the contribution of supernumerary centrosomes to mitotic defects, their ...
Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis
Clonal hematopoiesis (CH) is a phenomenon of clonal expansion of hematopoietic stem cells driven by somatic mutations affecting certain genes. Recently, CH has been linked to the development of hematologic malignancies, ...
Synthesis and properties of small interfering RNA duplexes carrying 5-ethyluridine residues
Oligoribonucleotides carrying 5-ethyluridine units were prepared using solid-phase phosphoramidite chemistry. The introduction of the tert-butyldimethylsilyl group at the 2'-OH position proceeded in good yield and very ...
RINGO/Speedy proteins, a family of non-canonical activators of CDK1 and CDK2
Cyclin-dependent kinases (CDKs) require the binding to a regulatory subunit to acquire enzymatic activity, and cyclins are the canonical CDK activators. However, there are specific situations in which CDKs can be activated ...
The epidermal circadian clock integrates and subverts brain signals to guarantee skin homeostasis
In mammals, the circadian clock network drives daily rhythms of tissue-specific homeostasis. To dissect daily inter-tissue communication, we constructed a mouse minimal clock network comprising only two nodes: the peripheral ...
Exploring the early stages of chemical unfolding of proteins at the proteome scale
After decades of using urea as denaturant, the kinetic role of this molecule in the unfolding process is still undefined: does urea actively induce protein unfolding or passively stabilize the unfolded state? By analyzing ...
Modulation of the helical properties of DNA: next-to-nearest neighbour effects and beyond
We used extensive molecular dynamics simulations to study the structural and dynamic properties of the central d(TpA) step in the highly polymorphic d(CpTpApG) tetranucleotide. Contrary to the assumption of the dinucleotide-model ...
The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2
Chemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the ...
Variable efficiency of nonsense-mediated mRNA decay across human tissues, tumors and individuals
BackgroundNonsense-mediated mRNA decay (NMD) is a quality-control pathway that degrades mRNA bearing premature termination codons (PTCs) resulting from mutation or mis-splicing, and that additionally participates in gene ...
Neuregulin, an effector on mitochondria metabolism that preserves insulin sensitivity
Various external factors modulate the metabolic efficiency of mitochondria. This review focuses on the impact of the growth factor neuregulin and its ErbB receptors on mitochondria and their relationship with several ...
