Papers by Juan C Paniagua
Inclou gasos ideals, mescles de gasos, pressió de vapor i una petita incursió en els gasos reals.... more Inclou gasos ideals, mescles de gasos, pressió de vapor i una petita incursió en els gasos reals.Breu recull de les propietats dels gasos amb exercicis
Nature Communications, Jun 7, 2023
The neurotensin receptor 1 (NTS 1 ) is a G protein-coupled receptor (GPCR) with promise as a drug... more The neurotensin receptor 1 (NTS 1 ) is a G protein-coupled receptor (GPCR) with promise as a drug target for the treatment of pain, schizophrenia, obesity, addiction, and various cancers. A detailed picture of the NTS 1 structural landscape has been established by X-ray crystallography and cryo-EM and yet, the molecular determinants for why a receptor couples to G protein versus arrestin transducers remain poorly defined. We used 13 C ε H 3 -methionine NMR spectroscopy to show that binding of phosphatidylinositol-4,5-bisphosphate (PIP2) to the receptor's intracellular surface allosterically tunes the timescale of motions at the orthosteric pocket and conserved activation motifswithout dramatically altering the structural ensemble. β-arrestin-1 further remodels the receptor ensemble by reducing conformational exchange kinetics for a subset of resonances, whereas G protein coupling has little to no effect on exchange rates. A β-arrestin biased allosteric modulator transforms the NTS 1 :G protein complex into a concatenation of substates, without triggering transducer dissociation, suggesting that it may function by stabilizing signaling incompetent G protein conformations such as the non-canonical state. Together, our work demonstrates the importance of kinetic information to a complete picture of the GPCR activation landscape. Cells rely on membrane-embedded receptors to maintain awareness of the extracellular environment without compromising membrane integrity. The G protein-coupled receptor (GPCR) superfamily is the largest group among such eukaryotic cell surface receptors, comprising more than 800 proteins 1,2 . They are ubiquitously expressed throughout the human body and are pivotal in a broad range of physiological processes including vision, taste, sense of smell, nervous functions, immune regulation, reproduction, and cancer . Ligand
Physical Chemistry Chemical Physics, 2016
Spherical nanoparticles and fibres observable by cryo-electron microscopy are spontaneously forme... more Spherical nanoparticles and fibres observable by cryo-electron microscopy are spontaneously formed by the Finland trityl radical at concentrations above 15 mM. These species represent a new class of paramagnetic, metal-free, nanoscale supramolecular materials. Selfassociation was observed under a variety of experimental conditions, including aqueous solution at room temperature, low temperature frozen glasses and the gas phase. Oligomers formed by at least 5 Finland radicals were detected by ion-mobility mass spectrometry. Magnetic susceptibility data as well as low temperature EPR spectra show coupling between electronic spins in the self-assembled species. Quantum chemical calculations show stacking along the C3 symmetry axis. Nanoparticle formation requires additional lateral packing that can be provided by bydrogen bonding involving the triangular array of carboxylic acid groups leading to the assembly of geodesic spheres.
bioRxiv (Cold Spring Harbor Laboratory), Nov 27, 2022
The neurotensin receptor 1 (NTS1) is a G protein-coupled receptor (GPCR) with promise as a drug t... more The neurotensin receptor 1 (NTS1) is a G protein-coupled receptor (GPCR) with promise as a drug target for the treatment of pain, schizophrenia, obesity, addiction, and various cancers. A detailed picture of the NTS1 structural landscape has been established by X-ray crystallography and cryo-EM and yet, the molecular determinants for why a receptor couples to G protein versus arrestin transducers remain poorly defined. We used 13 C ε H3methionine NMR spectroscopy to show that phosphatidylinositol-4,5-bisphosphate (PIP2) promotes transducer complexation not by dramatically altering the receptor structure but by strengthening long-range allosteric connections, in the form of correlated conformational kinetics, between the orthosteric pocket and highlyconserved activation motifs. β-arrestin-1 further remodels the receptor ensemble by reducing conformational exchange kinetics for a subset of resonances, whereas G protein coupling has little to no effect on the rate. A βarrestin biased allosteric modulator transforms the NTS1:G protein complex into a concatenation of substates, without triggering transducer dissociation, suggesting that it may function by stabilizing signaling incompetent G protein conformations such as the non-canonical state. Together, our work demonstrates the importance of kinetic information to a complete picture of the GPCR activation landscape.
SummaryUnlike many signaling proteins that function as binary switches between ‘on and off’ state... more SummaryUnlike many signaling proteins that function as binary switches between ‘on and off’ states, G protein-coupled receptors (GPCRs) exhibit basal activity that can be increased or decreased by numerous ligands. A given receptor can recognize multiple ligands, allosteric modulators, and transducers to create a complex free energy landscape. Many of the lowest energy states have been captured by static structural techniques while detailing the wells’ widths, metastable states, and the transition between them, is still in its infancy. Nuclear magnetic resonance (NMR) spectroscopy can monitor the structure and dynamics of GPCR ensembles across fifteen orders-of-magnitude, but technical challenges have limited its application to super-microsecond timescales. Focusing on a prototypical peptide-binding GPCR, the neurotensin receptor 1 (NTS1), we employed NMR and density functional theory (DFT) to probe global sub-nanosecond motions. The near random coil chemical shifts of the apo recep...
Arithmetic operations 6 class 2 () ** *, /, //, % +, -what does a+b/c**2 mean? (a+b)/(c+d) from l... more Arithmetic operations 6 class 2 () ** *, /, //, % +, -what does a+b/c**2 mean? (a+b)/(c+d) from left to right: a/2*b = (a/2)*b from right to left if there are more than one: a**2**3=a**8 higher priority order of execution a + b c 2 , a + b c 2 , a
Aquest document està subjecte a la llicència de Reconeixement-NoComercial-SenseObraDerivada de Cr... more Aquest document està subjecte a la llicència de Reconeixement-NoComercial-SenseObraDerivada de Creative Com mons, el text de la qual està disponible a: . Aquesta publicació ha rebut l'ajut de la Generalitat de Catalunya. Els noms comercials que apareixen en el text són marques registrades.
Ordinador: màquina capaç d'entendre instruccions externes per realitzar una tasca, fer-la i mostr... more Ordinador: màquina capaç d'entendre instruccions externes per realitzar una tasca, fer-la i mostrar-ne el resultat (versatilitat!) Maquinari: components físics de l'ordinador; és a dir, tot allò que es pot tocar Programari: instruccions (components lògics) que permeten manipular el maquinari en la forma desitjada. Informació Obriu la Carpeta de l'usuari. Obriu l'editor de textes (llàpis i llibreta). Escriviu un text, esborreu, copieu fragments, inserteu, etc. Deseu-lo en un fitxer anomenat prova ubicat a la Carpeta de l'usuari. Cliqueu a la finestra de la Carpeta de l'usuari i creeu-hi una carpeta anomenada exercicis. Arrossegueu el fitxer prova a la carpeta exercicis. Endolleu un pen drive i cliqueu-hi. Copieu el fitxer prova en el pen drive i desmunteu-lo (cliqueu amb el botó dret i seleccioneu Desmunta).
General angular momentum 36 9 a complete set of eigenvectors of Particular cases: •orbital angula... more General angular momentum 36 9 a complete set of eigenvectors of Particular cases: •orbital angular momentum L: j = l = 0, 1, 2, … •spin angular momentum S (electrons) or I (nuclei): j (s or I) takes a single value for each particle among: 0, 1/2, 1, 3/2, … For electrons s =1/2 and c J ± j,m j = ~qj(j + 1) m j (m j ± 1) j,m j ±1 Solution of the exercise 1.4
* This document was written for the subject Mathematical Foundations of Quantum Mechanics of the ... more * This document was written for the subject Mathematical Foundations of Quantum Mechanics of the Máster Interuniversitario en Química Teórica y Modelización Computacional. It is published under the Attribution 4.
Angewandte Chemie, Apr 6, 2010
Bioengineering, Biomaterials, and NanoMedicine (CIBER-BBN), promoted by ISCIII, Spain. V.M. ackno... more Bioengineering, Biomaterials, and NanoMedicine (CIBER-BBN), promoted by ISCIII, Spain. V.M. acknowledges the MICINN-Spain for a Juan de la Cierva postdoctoral contract and JCP thanks F. Mota for discussions and help in solving computational problems. Preliminary data were acquired in Birmingham with support from EU-NMR. Computations were carried out at the Centre de Supercomputació de Catalunya (CESCA) through a grant from the Universitat de Barcelona.
Physical Chemistry Chemical Physics, 2015
The OX63 radical forms supramolecular capsules hosting tetraalkylammonium cations. Extensive self... more The OX63 radical forms supramolecular capsules hosting tetraalkylammonium cations. Extensive self-association is also observed under standard dynamic nuclear polarization conditions.
Bioengineering, Biomaterials, and NanoMedicine (CIBER-BBN), promoted by ISCIII, Spain. V.M. ackno... more Bioengineering, Biomaterials, and NanoMedicine (CIBER-BBN), promoted by ISCIII, Spain. V.M. acknowledges the MICINN-Spain for a Juan de la Cierva postdoctoral contract and JCP thanks F. Mota for discussions and help in solving computational problems. Preliminary data were acquired in Birmingham with support from EU-NMR. Computations were carried out at the Centre de Supercomputació de Catalunya (CESCA) through a grant from the Universitat de Barcelona.
Theoretica chimica acta, 1983
Intrinsic and external 7r-orbital localization procedures which rely only on molecular topology a... more Intrinsic and external 7r-orbital localization procedures which rely only on molecular topology are proposed and discussed. Localized molecular orbitals obtained by application of these procedures are referred to as "topological localized molecular orbitals'.
Journal of Molecular Structure-theochem, Sep 1, 1996
This paper analyzes the changes experienced by the valence localized molecular orbitals (LMOs) of... more This paper analyzes the changes experienced by the valence localized molecular orbitals (LMOs) of benzene, singlet cyclobutadiene and (E)-1,3,Shexatriene-with respect to both energy and degree of delocalization-under the effect of several geometrical distortions of the carbon-carbon frame. The analysis shows that, at the AM1 level of theory, there is a unique symmetrizing tendency of the x-LMOs of benzene, which are at the same time maximally delocalized and energetically most stable for a totally symmetric geometry. The x-LMOs of both cyclobutadiene and hexatriene show opposite behavior, increasing their energies when subjected to bond length equalizing distortions and decreasing them when the carbon-carbon bond length alternation of the system is enhanced. The distortive properties of the x-electrons, when analyzed in terms of the corresponding AMl-LMOs, thus appear to correlate well with the aromatic character of the molecule.
International Journal of Quantum Chemistry, Sep 1, 1984
The multiple bond description supplied by localized molecular orbitals obtained within the ZDO ap... more The multiple bond description supplied by localized molecular orbitals obtained within the ZDO approximation is analyzed. In particular, conditions for the appearance of m-T separation and of continuous degeneracy of the localization sum against u-T mixing are given for two current ZDO energy-and density-localization methods. Likewise, a convenient modification of the latter is presented together with some illustrative examples.
International Journal of Quantum Chemistry, 1997
Electronic energy partitionings resulting from the classification of occupied molecular orbitals ... more Electronic energy partitionings resulting from the classification of occupied molecular orbitals in disjoint subsets are seen to be consistent with localization procedures preserving that classification, regardless of the treatment given to the crossing terms between different subsets. To illustrate the utility of this result, the electronic energies of pyrazole and imidazole are partitioned intoand-localized molecular orbital energy contributions, and the results are related with the aromaticity and basicity differences between both heterocycles.
Journal of Organic Chemistry, Mar 1, 1991
In the present work, an extensive study of the ~-1oCalized molecular orbitals of a set of 80 poly... more In the present work, an extensive study of the ~-1oCalized molecular orbitals of a set of 80 polycyclic hydrocarbons has been undertaken in order to clarify the relationship between resonance energies, local aromaticity, and electronic delocalization. A simple way of obtainii local remnance energies corresponding to bonds or rings is given; addition of these local resonance energies reproduces the global resonance energy of the system. According to the present analysis, aromaticity in altemant systems is consistently related to local electronic delocalization. In nonaltemant systems, however, local electronic delocalization is affected by charge separation and cannot be systematically related to aromaticities.
Journal of Molecular Structure-theochem, Jun 1, 1988
The pairing theorem, holding for canonical HUckel orbitals of alternant hydrocarbons, is shown to... more The pairing theorem, holding for canonical HUckel orbitals of alternant hydrocarbons, is shown to be extens4ble to any set of non-canonical molecular orbitals and, in particular, for a localized set. This allows to obtain antibonding counterparts of the occupied localized orbitals without having to repeat the localization procedure for the virtual set. Some particularities arising for charged systems are discussed, and the results obtained for naphthalene are shown as an example.
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Papers by Juan C Paniagua