A5046444163- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Monoclonal and Polyclonal Antibodies Research
- Neurotransmitter Receptor Influence on Behavior
- Chemical Synthesis and Analysis
- Lipid Membrane Structure and Behavior
- Photoreceptor and optogenetics research
- Computational Drug Discovery Methods
- Adenosine and Purinergic Signaling
- Protein Structure and Dynamics
- Cannabis and Cannabinoid Research
- Nicotinic Acetylcholine Receptors Study
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Protein Kinase Regulation and GTPase Signaling
- Hypothalamic control of reproductive hormones
- Drug Transport and Resistance Mechanisms
- Neurobiology and Insect Physiology Research
- Synthesis and Biological Evaluation
- Thyroid Disorders and Treatments
- Mass Spectrometry Techniques and Applications
- Biochemical Analysis and Sensing Techniques
- Chemokine receptors and signaling
Universitat Autònoma de Barcelona
2015-2024
National Institute on Drug Abuse
2023
National Institutes of Health
2023
Bellvitge University Hospital
2023
Universitat de Barcelona
1989-2023
Institut de Biomedicina de la Universitat de Barcelona
2023
Universidad Complutense de Madrid
2002-2020
Child Trends
2018-2019
General Department of Preventive Medicine
1992-2014
Icahn School of Medicine at Mount Sinai
1990-2009
Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety negative effects with major consequences in cannabis users that constitute important drawbacks for the use cannabinoids as therapeutic agents. For this reason, there is tremendous medical interest harnessing beneficial THC. Behavioral studies carried out mice lacking 5-HT2A (5-HT2AR) revealed remarkable 5-HT2AR-dependent dissociation antinociceptive THC and its detrimental amnesic...
G protein-coupled receptors (GPCRs) exist within a landscape of interconvertible conformational states and in dynamic equilibrium between monomers higher-order oligomers, both influenced by ligand binding. Here, we show that homobivalent formed equal chromenopyrazole moieties as pharmacophores, connected 14 methylene units, can modulate the dynamics cannabinoid CB
AMBER force fields are among the most commonly used in molecular dynamics (MD) simulations of proteins. Unfortunately, they lack a specific set lipid parameters, thus limiting its use membrane protein simulations. In order to overcome this limitation we assessed whether widely united-atom parameters described by Berger and co-workers could be conjunction with Thus, free energies solvation water cyclohexane, cyclohexane transfer, were computed thermodynamic integration procedures for neutral...
Abstract G protein-coupled receptors (GPCRs), proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether ligand-dependent interactions between these molecules are based on random collisions or rearrangement pre-coupled elements in a macromolecular complex. Furthermore, remains controversial GPCR homodimer coupled to single heterotrimeric protein constitutes common functional unit. Using peptide-based approach, we...
G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental transfer extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact heteromers novel units. Despite exponential growth number solved GPCR crystal structures, structural properties remain unknown. We used single-particle tracking experiments cells expressing functional adenosine A1-A2A fused fluorescent proteins show loss Brownian...
Abstract The binding process through the membrane bilayer of lipid-like ligands to a protein target is an important but poorly explored recognition at atomic level. In this work we succeeded in resolving lipid inhibitor ML056 sphingosine-1-phosphate receptor 1 (S1P R) using unbiased molecular dynamics simulations with aggregate sampling over 800 μs. pathway multi-stage consisting ligand diffusing leaflet contact “membrane vestibule” top TM 7, subsequently moving from lipid-facing vestibule...
G-protein-coupled receptor (GPCR) heteromeric complexes have distinct properties from homomeric GPCRs, giving rise to new functionalities. Adenosine receptors (A1R or A2AR) can form A1R-A2AR heteromers (A1-A2AHet), and their activation leads canonical G-protein-dependent (adenylate cyclase mediated) -independent (β-arrestin signaling. has different affinities for A1R A2AR, allowing the detect its concentration by integrating downstream Gi- Gs-dependent signals. cAMP accumulation β-arrestin...
The central adenosine system and receptors play a fundamental role in the modulation of dopaminergic neurotransmission. This is mostly achieved by strategic co-localization different dopamine receptor subtypes two populations striatal efferent neurons, striatonigral striatopallidal, that give rise to direct indirect pathways, respectively. With optogenetic techniques it has been possible dissect differential pathways mediating "Go" responses upon exposure reward-related stimuli "NoGo"...
Catalyst/HypoGen pharmacophore modeling approach and three-dimensional quantitative structure−activity relationship (3D-QSAR)/comparative molecular similarity indices analysis (CoMSIA) methods have been successfully applied to explain the cytotoxic activity of a set 51 natural synthesized naphthoquinone derivatives tested in human promyelocytic leukemia HL-60 cell line. The computational models facilitated identification structural elements ligands that are key for antitumoral properties....
G protein-coupled receptor (GPCR) heteromers are macromolecular complexes with unique functional properties different from those of its individual protomers. Little is known about what determines the quaternary structure GPCR resulting in their properties. In this study, using resonance energy transfer techniques experiments mutated receptors, we provide for first time clear evidence a key role intracellular domains determination between adenosine A2A, cannabinoid CB1, and dopamine D2...
The important and diverse biological functions of β-adrenergic receptors (βARs) have promoted the search for compounds to stimulate or inhibit their activity. In this regard, unraveling molecular basis ligand binding/unbinding events is essential understand pharmacological properties these G protein-coupled receptors. study, we use steered dynamics simulation method describe, in atomic detail, unbinding process two inverse agonists, which been recently co-crystallized with β1 β2ARs subtypes,...
Abstract Motivation: Integral polytopic membrane proteins contain only two types of folds in their transmembrane domains: α-helix bundles and β-barrels. The increasing number available crystal structures these permits an initial estimation how sequence variability affects the structure conservation domains. We, thus, aim to determine pairwise identity necessary maintain molecular architectures compatible with hydrophobic nature lipid bilayer. Results: Root-mean-square deviation (rmsd) were...
It has been hypothesized that heteromers of adenosine A2A receptors (A2AR) and cannabinoid CB1 (CB1R) localized in glutamatergic nerve terminals mediate the integration endocannabinoid signaling involved modulation striatal excitatory neurotransmission. Previous studies have demonstrated existence A2AR-CB1R artificial cell systems. A dependence A2AR for Gi protein-mediated CB1R was described as one its main biochemical characteristics. However, recent questioned localization functionally...
Abstract Background and Purpose Allosterism is a regulatory mechanism for GPCRs that can be attained by ligand‐binding or protein–protein interactions with another GPCR. We have studied the influence of dimer interface on allosteric properties A 2A receptor CB 2 heteromer. Experimental Approach evaluated cAMP production, phosphorylation signal‐regulated kinases (pERK1/2), label‐free dynamic mass redistribution, β‐arrestin recruitment bimolecular fluorescence complementation assays in absence...