29 papers · ranked by Valyu relevance
Jingjie Ning, Xiangzhen Shen, Li Hou, Shiyi Shen + 7 more
G proteincoupled receptors (GPCRs) govern diverse physiological processes and are central to modern pharmacology. Yet discovering GPCR modulators remains challenging because receptor activation often arises from complex allosteric effects rather than direct binding affinity, and conventional assays are slow, costly…
Irene Fasciani, Marco Carli, Francesco Petragnano, Francesco Colaianni + 5 more
'Francesco Colaianni' 'Gabriella Aloisi' 'Roberto Maggio' 'Marco Scarselli' 'Mario Rossi' 'Myron Szewczuk'] The architecture of eukaryotic cells is defined by extensive membrane-delimited compartments, which entails separate metabolic processes that would otherwise interfere with each other, leading to functional…
Giulia Palladino, Rafael Patarra, Zhenke Li, Moritz J. Rossner + 1 more
G protein-coupled receptors (GPCRs) are major drug targets for neurodegenerative, neurodevelopmental and psychiatric disorders and are targeted by a multitude of marketed drugs. Typically, multiple GPCRs are involved in diseases of this type, making precise modulation of these receptors crucial for beneficial responses…
Sathvik Anantakrishnan, Athi N. Naganathan
G-protein-coupled receptors (GPCRs) are ubiquitous integral membrane proteins involved in diverse cellular signaling processes and consequently serve as crucial drug targets. Here, we carry out the first large-scale ensemble thermodynamic study of 45 different ligand-free GPCRs employing a structure-based statistical…
Brix Mücher, Aida Garrido-Charles, Lukas Cyganek, Tobias Bruegmann + 3 more
Activation of G protein coupled receptors coupling to the G_i/o_ pathway leads to the activation of G protein-activated inward rectifier potassium channels (GIRK) in a fast membrane-delimited manner in excitable cells. Activation of GIRK causes the hyperpolarization of the cell membrane, where hyperpolarization is…
Khodeza Begum, Jonathon E Mohl, Fredrick Ayivor, Eder E Perez + 1 more
'Ming-Ying Leung'] Title: Abstract G protein-coupled receptors (GPCRs) constitute the largest group of membrane receptor proteins in eukaryotes. Due to their significant roles in various physiological processes such as vision, smell and inflammation, GPCRs are the targets of many prescription drugs. However, the…
Kilic Isildayancan, Amit Kessel, Ron Solan, Rachel Kolodny + 1 more
Currently known G protein-coupled receptors (GPCRs) have a single transmembrane domain. Many GPCRs form dimers that have two transmembrane domains (one per protein), and there are indications that this dimeric interaction is functionally meaningful. Here, based on sequence analysis and structure predictions, we report…
Hung N Do, Allan Haldane, Ronald M Levy, Yinglong Miao
G-protein-coupled receptors (GPCRs) are the largest family of human membrane proteins and represent the primary targets of about one third of currently marketed drugs. Despite the critical importance, experimental structures have been determined for only a limited portion of GPCRs and functional mechanisms of GPCRs…
Anil Annamneedi, Caroline Gora, Ana Dudas, Xavier Leray + 3 more
'Véronique Bozon' 'Pascale Crépieux' 'Lucie P. Pellissier'] Changes in genetic and/or environmental factors to developing neural circuits and subsequent synaptic functions are known to be a causative underlying the varied socio-emotional behavioural patterns associated with autism spectrum disorders (ASD). Seven…
Elise Wouters, Lakshmi Vasudevan, René A. J. Crans, Deepak K. Saini + 1 more
'Christophe P. Stove'] G protein-coupled receptors (GPCRs) have the propensity to form homo- and heterodimers. Dysfunction of these dimers has been associated with multiple diseases, e.g., pre-eclampsia, schizophrenia, and depression, among others. Over the past two decades, considerable efforts have been made towards…
Valentina Fernandez-Figueroa, Camila A. Quercia-Raty, Jan Gallastegui-Ulloa, Luka Robeson + 1 more
G-protein coupled receptors (GPCRs) are responsible for translating environmental signals of various types into cellular signals. Over 40 thousand GPCR orthologs have been discovered in the supergroup Unikonta, and around 800 genes encode for GPCRs in the human genome. In contrast to this astonishing variety, only a…
Marco A. Alfonzo-Méndez, Rocío Alcántara-Hernández, J. Adolfo García-Sáinz, Kathleen Van Craenenbroeck
'J. Adolfo García-Sáinz' 'Kathleen Van Craenenbroeck'] Background: Upon natural agonist or pharmacological stimulation, G protein-coupled receptors (GPCRs) are subjected to posttranslational modifications, such as phosphorylation and ubiquitination. These posttranslational modifications allow protein-protein…
Garima Chib, Parisa Mollaei, Amir Barati Farimani
G-Protein Coupled Receptors (GPCRs) are integral to numerous physiological processes and are the target of approximately one-third of FDA-approved therapeutics. Despite their significance, only a limited subset of GPCRs has been successfully targeted, primarily due to challenges in accurately modeling their structures.…
Siri Leemann, Sonja Kleinlogel
G-protein coupled receptors (GPCRs) are the largest family of human receptors that transmit signals from natural ligands and pharmaceutical drugs into essentially every physiological process. One main characteristic of GPCRs is their ability to specifically couple with different families of G-proteins, thereby…
Guan-Da Syu, Shih-Chin Wang, Guangzhong Ma, Shuang Liu + 15 more
G protein-coupled receptors (GPCRs) comprise the largest membrane protein family in humans and can respond to a wide variety of ligands and stimuli. Like other multi-pass membrane proteins, the biochemical properties of GPCRs are notoriously difficult to study because they must be embedded in lipid bilayers to maintain…
Alain Garcia De Las Bayonas, Nicole King
G protein-coupled receptors (GPCRs) play a pivotal role in the perception of environmental cues across eukaryotic diversity. Although GPCRs have been relatively well characterized in metazoans, GPCR signaling is poorly understood in their sister group, the choanoflagellates, and in other close relatives of metazoans…
Roberto Maggio, Irene Fasciani, Marco Carli, Francesco Petragnano + 4 more
'Francesco Marampon' 'Mario Rossi' 'Marco Scarselli' 'Mark S. Johnson'] Information flow from a source to a receiver becomes informative when the recipient can process the signal into a meaningful form. Information exchange and interpretation is essential in biology and understanding how cells integrate signals from a…
Authors not listed
G-protein-coupled receptors (GPCRs)—primary targets for over one-third of approved therapeutics—rely on intricate conformational transitions to transduce signals. While Molecular Dynamics (MD) is essential for elucidating this transduction process, particularly within ligand-bound complexes, conventional all-atom MD…
Jesse A Port, Micaela S Parker, Robin B Kodner, James C Wallace + 2 more
'E Virginia Armbrust' 'Elaine M Faustman'] Background The G protein-coupled receptor (GPCR) signaling pathway plays an essential role in signal transmission and response to external stimuli in mammalian cells. Protein components of this pathway have been characterized in plants and simpler eukaryotes such as yeast, but…
Stefano Costanzi
G protein-coupled receptors, or GPCRs, are a large superfamily of proteins found on the plasma membrane of cells. They are involved in most physiological and pathophysiological functions and constitute the target of the majority of marketed drugs. Although these receptors have been historically elusive to attempts of…
Sebastian Raschka
While G-protein coupled receptors (GPCRs) constitute the largest class of membrane proteins, structures and endogenous ligands of a large portion of GPCRs remain unknown. Due to the involvement of GPCRs in various signaling pathways and physiological roles, the identification of endogenous ligands as well as designing…
Sebastian Raschka, Benjamin Kaufman
In the last decade, machine learning and artificial intelligence applications have received a significant boost in performance and attention in both academic research and industry. The success behind most of the recent state-of-the-art methods can be attributed to the latest developments in deep learning. When applied…
Yoonji Lee, Sun Choi, Changbong Hyeon
Dynamics and functions of G-protein coupled receptors (GPCRs) are accurately regulated by the type of ligands that bind to the orthosteric or allosteric binding sites. To glean the structural and dynamical origin of ligand-dependent modulation of GPCR activity, we performed total ∼ 5 µsec molecular dynamics simulations…
Authors not listed
GPR3 belongs to the protein superfamily of G protein-coupled receptors (GPCRs) and plays a central role in both benign and malignant physiological processes, such as energy expenditure in adipocytes and Alzheimer’s disease pathology, respectively. Despite the therapeutic potential of both receptor agonists and inverse…
Authors not listed
Pandemics, such as Influenza and Covid-19, highlight the global challenge of controlling viral outbreaks. Despite the rapid development of vaccines for SARS-CoV 2, current antiviral treatments are not broadly effective against diverse strains. Thus, there is an urgent need to develop vaccines targeting Covid-19 and…
Lara Toy, Max E. Huber, Maximilian F. Schmidt, Dorothee Weikert + 1 more
Fluorescently labeled ligands are versatile molecular tools to study G protein-coupled receptors (GPCRs) and can be used for a range of different applications, including bioluminescence resonance energy transfer (BRET) assays. Here, we report the structure-based development of fluorescent ligands targeting the…
Authors not listed
Allosteric modulators offers a promising approach for targeting receptor function in pathological contexts. Although numerous orthosteric ligands have been developed, the discovery of allosteric inhibitors remains limited, hindered by challenges with identifying modulators and the perceived lower druggability of…
Marina Gorostiola González, Remco L. van den Broek, Thomas G.M. Braun, Magdalini Chatzopoulou + 4 more
Proteochemometric (PCM) modelling is a powerful computational drug discovery tool used in bioactivity prediction of potential drug candidates relying on both chemical and protein information. In PCM features are computed to describe small molecules and proteins, which directly impact the quality of the predictive…
Christoph Haag, Julia Erl, Korbinian Helbig, Joachim Wegener + 1 more
Cyclic adenosine monophosphate (cAMP) is one of the most prominent molecules involved in intracellular signaling. As a second messenger, it regulates a plethora of biochemical processes that are essential to keep a cell alive and orchestrates physiological responses to external stimuli. Ever since its discovery, great…