2025
T‑ALPHA: A Hierarchical Transformer-Based Deep Neural Network for Protein–Ligand Binding Affinity Prediction with Uncertainty-Aware Self-Learning for Protein-Specific Alignment
Kyro G, Smaldone A, Shee Y, Xu C, Batista V. T‑ALPHA: A Hierarchical Transformer-Based Deep Neural Network for Protein–Ligand Binding Affinity Prediction with Uncertainty-Aware Self-Learning for Protein-Specific Alignment. Journal Of Chemical Information And Modeling 2025, 65: 2395-2415. PMID: 39965912, DOI: 10.1021/acs.jcim.4c02332.Peer-Reviewed Original ResearchConceptsProtein-ligand binding affinity predictionBinding affinity predictionState-of-the-art performanceTransformer-based deep neural networksMultimodal feature representationAffinity predictionBinding affinity of small moleculesState-of-the-artDeep neural networksDeep learning modelsAffinity of small moleculesSelf-learning methodSARS-CoV-2 main proteasePredicted binding affinitiesFeature representationBinding affinityOn-target potencyNeural networkDrug discovery applicationsTransformation frameworkLearning modelsScoring functionCrystal structureSelf-learningMain protease[18F]MK-6240 Radioligand Delivery Indices as Surrogates of Cerebral Perfusion: Bias and Correlation Against [15O]Water.
Fu J, Juttukonda M, Garimella A, Salvatore A, Lois C, Ranasinghe A, Efthimiou N, Sari H, Aye W, Guehl N, El Fakhri G, Johnson K, Dickerson B, Izquierdo-Garcia D, Catana C, Price J. [18F]MK-6240 Radioligand Delivery Indices as Surrogates of Cerebral Perfusion: Bias and Correlation Against [15O]Water. Journal Of Nuclear Medicine 2025, 66: 410-417. PMID: 39947916, PMCID: PMC11876731, DOI: 10.2967/jnumed.124.268701.Peer-Reviewed Original Research
2024
Photosystem II: light-dependent oscillation of ligand composition at its active site
Wang J. Photosystem II: light-dependent oscillation of ligand composition at its active site. Acta Crystallographica Section D, Structural Biology 2024, 80: 850-861. PMID: 39607822, DOI: 10.1107/s2059798324011392.Peer-Reviewed Original ResearchNeuroMark PET: Replicable positron emission tomography ICA templates for florbetapir and florbetaben radioligands
Eierud C, Fu Z, Petropoulos H, Bohsali A, Iraji A, Ganz M, Pernet C, Calhoun V. NeuroMark PET: Replicable positron emission tomography ICA templates for florbetapir and florbetaben radioligands. Annual International Conference Of The IEEE Engineering In Medicine And Biology Society (EMBC) 2024, 00: 1-4. PMID: 40039357, DOI: 10.1109/embc53108.2024.10782228.Peer-Reviewed Original ResearchAdvances and Insights in Positron Emission Tomography Tracers for Metabotropic Glutamate Receptor 4 Imaging
Wang J, Li Y, Fakhri G. Advances and Insights in Positron Emission Tomography Tracers for Metabotropic Glutamate Receptor 4 Imaging. Journal Of Medicinal Chemistry 2024, 67: 10517-10529. PMID: 38924702, PMCID: PMC11290609, DOI: 10.1021/acs.jmedchem.3c02431.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsPositron emission tomographyPositron emission tomography radioligandsAllosteric modulatorsMGluR4 positive allosteric modulatorsMetabotropic glutamate receptor subtype 4PET ligandNeurological disordersPositron emission tomography tracersEmission tomographySubtype 4Molecular imaging modalitiesEffective treatmentMetabotropicDisordersParent drugImaging modalitiesPET tracersMGluR4Therapeutic targetPositron emitting radioisotopesSelection of lead compoundsLiving subjectsPositronQuantitative accuracyDevelopment of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release
Zhou X, Stine C, Prada P, Fusca D, Assoumou K, Dernic J, Bhat M, Achanta A, Johnson J, Pasqualini A, Jadhav S, Bauder C, Steuernagel L, Ravotto L, Benke D, Weber B, Suko A, Palmiter R, Stoeber M, Kloppenburg P, Brüning J, Bruchas M, Patriarchi T. Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release. Nature Communications 2024, 15: 5353. PMID: 38918403, PMCID: PMC11199706, DOI: 10.1038/s41467-024-49712-0.Peer-Reviewed Original ResearchConceptsOpioid peptide releaseVentral tegmental areaAcute brain slicesN/OFQ actionsChemogenetic activationIn vivo studiesNociceptin/orphanin FQTegmental areaFibre photometryOpioid peptidesBrain slicesPharmacological profileGenetically encoded sensorIntracellular signal transducersReceptor ligandsPeptide releaseMammalian brainFunctional relevanceNeuronsBehavioral processesSignal transducerReleasePotential interactionsRegulatory functionsN/OFQAlphaFold2 structures guide prospective ligand discovery
Lyu J, Kapolka N, Gumpper R, Alon A, Wang L, Jain M, Barros-Álvarez X, Sakamoto K, Kim Y, DiBerto J, Kim K, Glenn I, Tummino T, Huang S, Irwin J, Tarkhanova O, Moroz Y, Skiniotis G, Kruse A, Shoichet B, Roth B. AlphaFold2 structures guide prospective ligand discovery. Science 2024, 384: eadn6354. PMID: 38753765, PMCID: PMC11253030, DOI: 10.1126/science.adn6354.Peer-Reviewed Original ResearchConceptsExperimental structuresLigand discoveryStructure-based drug designAlphaFold2 structuresAlphaFold2 modelsSample conformationsResidue conformationsDrug designLarge librariesDockingLigand recognitionLigandConformationLow energyStructureHit rateMoleculesAlphaFold2 predictionsTesting hundredsCryo-electron microscopy structureAlphaFold2Cryo-electronHitsCompare resultsEnergyStructure-based discovery of CFTR potentiators and inhibitors
Liu F, Kaplan A, Levring J, Einsiedel J, Tiedt S, Distler K, Omattage N, Kondratov I, Moroz Y, Pietz H, Irwin J, Gmeiner P, Shoichet B, Chen J. Structure-based discovery of CFTR potentiators and inhibitors. Cell 2024, 187: 3712-3725.e34. PMID: 38810646, PMCID: PMC11262615, DOI: 10.1016/j.cell.2024.04.046.Peer-Reviewed Original ResearchConceptsLarge-scale dockingIon channel drug discoveryStructure-based discoveryStructure-based optimizationMedicinal chemistryTested ligandsMolecular dockingSmall moleculesDrug discoveryCystic fibrosis transmembrane conductance regulatorMoleculesAllosteric siteIonsDockingLigandSecretory diarrheaCystic fibrosisCystic fibrosis transmembrane conductance regulator modulatorsChemistryTransmembrane conductance regulatorSuboptimal pharmacokineticsCFTR potentiatorsLeukocyte-associated immunoglobulin-like receptor-1 blockade in combination with programmed death-ligand 1 targeting therapy mediates increased tumour control in mice
Singh A, Mommers-Elshof E, Vijver S, Jansen J, Gonder S, Lebbink R, Bihan D, Farndale R, Boon L, Langermann S, Leusen J, Flies D, Meyaard L, Pascoal Ramos M. Leukocyte-associated immunoglobulin-like receptor-1 blockade in combination with programmed death-ligand 1 targeting therapy mediates increased tumour control in mice. Cancer Immunology, Immunotherapy 2024, 73: 16. PMID: 38236251, PMCID: PMC10796629, DOI: 10.1007/s00262-023-03600-6.Peer-Reviewed Original ResearchConceptsLeukocyte-associated immunoglobulin-like receptor-1Increase tumor controlTumor controlAnti-programmed death-ligand 1Mouse modelT cells in vitroMouse T cells in vitroIncreased tumor clearanceAnti-tumor responsesDeath-ligand 1Immunocompetent mouse modelReduced tumor burdenControl tumor growthHumanized mouse modelIn vivo tumor modelsWild type miceAssociated with tumor developmentPD-L1Tumor burdenTumor clearanceConventional immunotherapyImmunocompetent miceTumor outgrowthTherapy responseTumor microenvironment
2023
Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas
Youngblood M, Erson-Omay Z, Li C, Najem H, Coșkun S, Tyrtova E, Montejo J, Miyagishima D, Barak T, Nishimura S, Harmancı A, Clark V, Duran D, Huttner A, Avşar T, Bayri Y, Schramm J, Boetto J, Peyre M, Riche M, Goldbrunner R, Amankulor N, Louvi A, Bilgüvar K, Pamir M, Özduman K, Kilic T, Knight J, Simon M, Horbinski C, Kalamarides M, Timmer M, Heimberger A, Mishra-Gorur K, Moliterno J, Yasuno K, Günel M. Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas. Nature Communications 2023, 14: 6279. PMID: 37805627, PMCID: PMC10560290, DOI: 10.1038/s41467-023-41926-y.Peer-Reviewed Original ResearchAllosteric inhibition of the T cell receptor by a designed membrane ligand
Ye Y, Morita S, Chang J, Buckley P, Wilhelm K, DiMaio D, Groves J, Barrera F. Allosteric inhibition of the T cell receptor by a designed membrane ligand. ELife 2023, 12: e82861. PMID: 37796108, PMCID: PMC10554751, DOI: 10.7554/elife.82861.Peer-Reviewed Original ResearchConceptsT cell receptorTCR activationCD3ζ subunitsTM ligandsComplex molecular machinesReceptor tyrosine kinase EphA2Cell receptorTM domainTransmembrane domainNative nanodiscsTCR subunitsAllosteric changesTM bundleCytoplasmic sideTM regionMolecular mechanismsExtracellular domainAllosteric inhibitionLck phosphorylationMolecular machinesMembrane receptorsAberrant activationSubunitsMembrane ligandsDecades of investigationThe Concise Guide to PHARMACOLOGY 2023/24: Ion channels
Alexander S, Mathie A, Peters J, Veale E, Striessnig J, Kelly E, Armstrong J, Faccenda E, Harding S, Davies J, Aldrich R, Attali B, Baggetta A, Becirovic E, Biel M, Bill R, Caceres A, Catterall W, Conner A, Davies P, De Clerq K, Delling M, Di Virgilio F, Falzoni S, Fenske S, Fortuny-Gomez A, Fountain S, George C, Goldstein S, Grimm C, Grissmer S, Ha K, Hammelmann V, Hanukoglu I, Hu M, Ijzerman A, Jabba S, Jarvis M, Jensen A, Jordt S, Kaczmarek L, Kellenberger S, Kennedy C, King B, Kitchen P, Liu Q, Lynch J, Meades J, Mehlfeld V, Nicke A, Offermanns S, Perez-Reyes E, Plant L, Rash L, Ren D, Salman M, Sieghart W, Sivilotti L, Smart T, Snutch T, Tian J, Trimmer J, Van den Eynde C, Vriens J, Wei A, Winn B, Wulff H, Xu H, Yang F, Fang W, Yue L, Zhang X, Zhu M. The Concise Guide to PHARMACOLOGY 2023/24: Ion channels. British Journal Of Pharmacology 2023, 180: s145-s222. PMID: 38123150, PMCID: PMC11339754, DOI: 10.1111/bph.16178.Peer-Reviewed Original ResearchConceptsBest available pharmacological toolsOpen access knowledgebase sourceOfficial IUPHAR classificationAvailable pharmacological toolsDrug targetsG protein-coupled receptorsIon channelsProtein-coupled receptorsNomenclature guidanceClinical pharmacologyMajor pharmacological targetCatalytic receptorsSelective pharmacologyNuclear hormone receptorsPharmacological targetsPharmacological toolsHormone receptorsPrevious GuidesReceptorsLandscape formatHuman drug targetsPharmacologyConcise guideBiennial publicationRelated targetsTLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance
Çakan E, Kioon M, Garcia-Carmona Y, Glauzy S, Oliver D, Yamakawa N, Loza A, Du Y, Schickel J, Boeckers J, Yang C, Baldo A, Ivashkiv L, Young R, Staudt L, Moody K, Nündel K, Marshak-Rothstein A, van der Made C, Hoischen A, Hayward A, Rossato M, Radstake T, Cunningham-Rundles C, Ryu C, Herzog E, Barrat F, Meffre E. TLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance. Journal Of Experimental Medicine 2023, 220: e20230944. PMID: 37773045, PMCID: PMC10541333, DOI: 10.1084/jem.20230944.Peer-Reviewed Original ResearchConceptsCentral B cell toleranceB cell toleranceCell toleranceB cellsSystemic sclerosisTLR9 functionNovel therapeutic strategiesTLR9/MyD88Immature B cellsB cell receptorTolerogenic functionSSc patientsTLR9 expressionHumanized miceTLR9 responsesAutoreactive clonesTherapeutic strategiesChemokine CXCL4Cell receptorCXCL4Vivo productionTLR9MyD88ReceptorsCells8-oxoguanine riboswitches in bacteria detect and respond to oxidative DNA damage
Dhakal S, Kavita K, Panchapakesan S, Roth A, Breaker R. 8-oxoguanine riboswitches in bacteria detect and respond to oxidative DNA damage. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2307854120. PMID: 37748066, PMCID: PMC10556655, DOI: 10.1073/pnas.2307854120.Peer-Reviewed Original ResearchConceptsAptamer domainGene expressionLigand specificityOxidative damageLigand-binding pocketRiboswitch classesFamilies of bacteriaRare variantsRiboswitch aptamerCertain oxidative stressesExposure of cellsOxidative DNA damageRiboswitchGene associationsRNA aptamersDNA damageNucleotide poolBacteriaTarget ligandsOxidative stressMutationsNumerous alterationsPurine derivativesExpressionVariantsReceptor–ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology
Lau S, Fu A, Ip N. Receptor–ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology. Journal Of Neurochemistry 2023, 166: 891-903. PMID: 37603311, DOI: 10.1111/jnc.15933.Peer-Reviewed Original ResearchConceptsDanger-associated molecular patternsMicroglial chemotaxisAD pathogenesisAlzheimer's diseaseMicroglial functionRepertoire of surface receptorsHyperphosphorylated tauAlzheimer's disease pathologyAmyloid-betaMolecular machineryMicroglial receptorsReceptor-ligand interactionsPhagocytic clearanceReceptor-ligand axisMolecular patternsSurface receptorsFunctional transitionDisease pathologyChemotaxisBrain homeostasisAberrant synaptic pruningClearance activityCritical stepsReceptorsAmyloidThe minor chicken class I gene BF1 is deleted between short imperfect direct repeats in the B14 and typical B15 major histocompatibility complex (MHC) haplotypes
Rocos N, Coulter F, Tan T, Kaufman J. The minor chicken class I gene BF1 is deleted between short imperfect direct repeats in the B14 and typical B15 major histocompatibility complex (MHC) haplotypes. Immunogenetics 2023, 75: 455-464. PMID: 37405420, PMCID: PMC10514180, DOI: 10.1007/s00251-023-01313-9.Peer-Reviewed Original ResearchConceptsClass I genesCytotoxic T lymphocytesI geneNucleotide direct repeatChicken MHC haplotypesChicken major histocompatibility complexDirect repeatsHomologous genesTranscriptional orientationSplice sitePhenotypic effectsUntranslated regionChicken MHCBG genesB locusGenesHaplotypesB15 haplotypeMajor histocompatibility complexDeletionT lymphocytesCell ligandsRIG-I recognizes metabolite-capped RNAs as signaling ligands
Schweibenz B, Solotchi M, Hanpude P, Devarkar S, Patel S. RIG-I recognizes metabolite-capped RNAs as signaling ligands. Nucleic Acids Research 2023, 51: 8102-8114. PMID: 37326006, PMCID: PMC10450190, DOI: 10.1093/nar/gkad518.Peer-Reviewed Original ResearchConceptsRIG-IRNA endsRIG-I signaling pathwayIn vitro transcriptionRIG-I signalingDouble-stranded RNAInnate antiviral immune responseInterferon responseReceptor RIG-ICellular signaling assaysCapped RNACellular rolesPathogenic RNAsViral genomeEndogenous mRNAReplication intermediatesM7GSignaling ligandsImmune responseInnate immune receptor RIG-ISignaling pathwayRNASignaling assaysATPase activityAntiviral immune responseCD24-Siglec interactions in inflammatory diseases
Liu Y, Zheng P. CD24-Siglec interactions in inflammatory diseases. Frontiers In Immunology 2023, 14: 1174789. PMID: 37228622, PMCID: PMC10203428, DOI: 10.3389/fimmu.2023.1174789.Peer-Reviewed Original ResearchConceptsMultiple cell typesDifferential glycosylationRegulation of inflammatory diseasesBiological significanceSurface CD24Treat graft-vs-host diseaseMetabolic disordersInflammatory diseasesGraft-vs-host diseaseCell typesPhysiological functionsInflammatory response to tissue injurySiglecsResponse to tissue injuryRespiratory distressAutoimmune diseasesCD24Tissue injuryEndogenous ligandClinical translationGlycosylationDiseaseTranslational researchTudor–dimethylarginine interactions: the condensed version
Šimčíková D, Gelles-Watnick S, Neugebauer K. Tudor–dimethylarginine interactions: the condensed version. Trends In Biochemical Sciences 2023, 48: 689-698. PMID: 37156649, PMCID: PMC10524826, DOI: 10.1016/j.tibs.2023.04.003.Peer-Reviewed Original ResearchConceptsSurvival motor neuron (SMN) proteinTudor domainDiverse cellular functionsRNA-RNA interactionsSMN Tudor domainMotor neuron proteinCellular functionsProtein localizationProtein-RNASpinal muscular atrophyProtein ligandsNeuron proteinIntramolecular interactionsMuscular atrophyProteinInteractionFunctionLigandsModificationBiomolecularCellsLocalizationOpen questionDomainFormationBrief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in Programmed Cell Death-(Ligand)1–Monotherapy Pretreated, Advanced NSCLC: Results From a Phase 1b Clinical Trial
Garon E, Spira A, Goldberg S, Chaft J, Papadimitrakopoulou V, Cascone T, Antonia S, Brahmer J, Camidge D, Powderly J, Wozniak A, Felip E, Wu S, Ascierto M, Elgeioushi N, Awad M. Brief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in Programmed Cell Death-(Ligand)1–Monotherapy Pretreated, Advanced NSCLC: Results From a Phase 1b Clinical Trial. Journal Of Thoracic Oncology 2023, 18: 1094-1102. PMID: 37146752, DOI: 10.1016/j.jtho.2023.04.020.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerObjective response rateAdvanced non-small cell lung cancerTreatment-related adverse eventsBlinded independent central reviewIndependent central reviewRECIST v1.1Refractory patientsAdverse eventsCentral reviewRefractory non-small cell lung cancerCommon treatment-related adverse eventsSolid Tumors version 1.1Cell death protein 1End pointPhase 1b clinical trialEfficacy of durvalumabPhase 1b studyManageable safety profilePrimary end pointSecondary end pointsProgression-free survivalResponse Evaluation CriteriaMonths of treatmentDeath protein 1
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply