Raymond C. Stevens
YOU?
Author Swipe
View article: Structural basis for chemotype diversity in small molecule GLP-1 receptor agonist drug discovery
Structural basis for chemotype diversity in small molecule GLP-1 receptor agonist drug discovery Open
The glucagon-like peptide-1 receptor (GLP-1R) is an established therapeutic target for treating obesity and related diseases with several approved injectable peptide agonists on the market. Small molecule GLP-1R agonists, which offer great…
View article: Characterizing the role of extracellular domain in GLP-1R biased agonism
Characterizing the role of extracellular domain in GLP-1R biased agonism Open
The biased agonism of glucagon-like peptide-1 receptor (GLP-1R) plays a key role in the efficacy and side effects of drugs used to treat type II diabetes mellitus and obesity. Despite its therapeutic potential, the mechanisms underlying GL…
View article: Medial septum-dependent encoding of contextual inputs by hippocampal splitter cells
Medial septum-dependent encoding of contextual inputs by hippocampal splitter cells Open
The brain's ability to adapt to changing environments relies on encoding associations between stimuli and response strategies. Hippocampal splitter cells, which exhibit context-dependent firing patterns, are thought to contribute to this p…
View article: The 4<sup>th</sup>GPCR Dock: assessment of blind predictions for GPCR-ligand complexes in the era of AlphaFold
The 4<sup>th</sup>GPCR Dock: assessment of blind predictions for GPCR-ligand complexes in the era of AlphaFold Open
The GPCR Dock competitions are a series of community-wide assessments of computational structural modeling and ligand docking for G protein-coupled receptors, a central class of drug targets in the human proteome. The assessments are desig…
View article: In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography
In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography Open
Actin mediates insulin secretion in pancreatic β-cells through remodeling. Hampered by limited resolution, previous studies have offered an ambiguous depiction as depolymerization and repolymerization. We report the in situ structure of ac…
View article: Conformational Dynamics of the Activated GLP-1 Receptor-G<sub>s</sub> Complex Revealed by Cross-Linking Mass Spectrometry and Integrative Structure Modeling
Conformational Dynamics of the Activated GLP-1 Receptor-G<sub>s</sub> Complex Revealed by Cross-Linking Mass Spectrometry and Integrative Structure Modeling Open
Despite advances in characterizing the structures and functions of G protein-coupled receptors (GPCRs), our understanding of GPCR activation and signaling is still limited by the lack of information on conformational dynamics. It is partic…
View article: In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography
In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography Open
Actin mediates insulin secretion from the pancreatic β-cell through a remodeling process. Previous studies have been hampered by limited resolution, providing an ambiguous depiction of actin remodeling as a process that begins with depolym…
View article: Affinity selection of double-click triazole libraries for rapid discovery of allosteric modulators for GLP-1 receptor
Affinity selection of double-click triazole libraries for rapid discovery of allosteric modulators for GLP-1 receptor Open
The recently developed double-click reaction sequence [G. Meng et al. , Nature 574 , 86–89 (2019)] is expected to vastly expand the number and diversity of synthetically accessible 1,2,3-triazole derivatives. However, it remains elusive ho…
View article: Color and shape changing polymeric ribbons and sheets
Color and shape changing polymeric ribbons and sheets Open
The present invention herein provides the design, synthesis and characterization of compositions comprising asymmetric bolaamphiphilic lipids that form extended polymeric ribbons and wide sheets. These compositions may be doped, or intersp…
View article: GLP-1R Signaling and Functional Molecules in Incretin Therapy
GLP-1R Signaling and Functional Molecules in Incretin Therapy Open
Glucagon-like peptide-1 receptor (GLP-1R) is a critical therapeutic target for type 2 diabetes mellitus (T2DM). The GLP-1R cellular signaling mechanism relevant to insulin secretion and blood glucose regulation has been extensively studied…
View article: An intensity-based post-processing tool for 3D instance segmentation of organelles in soft X-ray tomograms
An intensity-based post-processing tool for 3D instance segmentation of organelles in soft X-ray tomograms Open
Investigating the 3D structures and rearrangements of organelles within a single cell is critical for better characterizing cellular function. Imaging approaches such as soft X-ray tomography have been widely applied to reveal a complex su…
View article: GPCR Agonist-to-Antagonist Conversion: Enabling the Design of Nucleoside Functional Switches for the A<sub>2A</sub> Adenosine Receptor
GPCR Agonist-to-Antagonist Conversion: Enabling the Design of Nucleoside Functional Switches for the A<sub>2A</sub> Adenosine Receptor Open
Modulators of the G protein-coupled A2A adenosine receptor (A2AAR) have been considered promising agents to treat Parkinson's disease, inflammation, cancer, and central nervous system disorders. Herein, we demonstrate that a thiophene modi…
View article: Quantitative, in situ visualization of intracellular insulin vesicles in pancreatic beta cells
Quantitative, in situ visualization of intracellular insulin vesicles in pancreatic beta cells Open
Characterizing relationships between Zn 2+ , insulin, and insulin vesicles is of vital importance to the study of pancreatic beta cells. However, the precise content of Zn 2+ and the specific location of insulin inside insulin vesicles are…
View article: Aerobic glycolysis imaging of epileptic foci during the inter-ictal period
Aerobic glycolysis imaging of epileptic foci during the inter-ictal period Open
This work was supported by ShanghaiTech University, the Shanghai Municipal Government, the National Natural Science Foundation of China Grant (No. 81950410637) and Shanghai Municipal Key Clinical Specialty (No. shslczdzk03403). F. H. and P…
View article: Auto-segmentation and time-dependent systematic analysis of mesoscale cellular structure in β-cells during insulin secretion
Auto-segmentation and time-dependent systematic analysis of mesoscale cellular structure in β-cells during insulin secretion Open
The mesoscale description of the subcellular organization informs about cellular mechanisms in disease state. However, applications of soft X-ray tomography (SXT), an important approach for characterizing organelle organization, are limite…
View article: Ligand-independent modulation of GIPR signaling by splice variants
Ligand-independent modulation of GIPR signaling by splice variants Open
Glucose-dependent insulinotropic polypeptide receptor (GIPR) is a potential drug target for metabolic disorders. It works with glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) in humans to maintain glucose homeostasis…
View article: Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades
Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades Open
Since their discovery, nicotinic acetylcholine receptors (nAChRs) have been extensively studied to understand their function, as well as the consequence of alterations leading to disease states. Importantly, these receptors represent pharm…
View article: Rational Remodeling of Atypical Scaffolds for the Design of Photoswitchable Cannabinoid Receptor Tools
Rational Remodeling of Atypical Scaffolds for the Design of Photoswitchable Cannabinoid Receptor Tools Open
Azobenzene-embedded photoswitchable ligands are the widely used chemical tools in photopharmacological studies. Current approaches to azobenzene introduction rely mainly on the isosteric replacement of typical azologable groups. However, a…
View article: Bayesian metamodeling of complex biological systems across varying representations
Bayesian metamodeling of complex biological systems across varying representations Open
Significance Cells are the basic units of life, yet their architecture and function remain to be fully characterized. This work describes Bayesian metamodeling, a modeling approach that divides and conquers a large problem of modeling nume…
View article: Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor
Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor Open
Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that exerts crucial metabolic functions by binding and activating its cognate receptor, GIPR. As an important therapeutic target, GIPR has been subjected to intensive …
View article: Live-cell imaging of glucose-induced metabolic coupling of β and α cell metabolism in health and type 2 diabetes
Live-cell imaging of glucose-induced metabolic coupling of β and α cell metabolism in health and type 2 diabetes Open
Type 2 diabetes is characterized by β and α cell dysfunction. We used phasor-FLIM (Fluorescence Lifetime Imaging Microscopy) to monitor oxidative phosphorylation and glycolysis in living islet cells before and after glucose stimulation. In…
View article: Bayesian metamodeling of complex biological systems across varying representations
Bayesian metamodeling of complex biological systems across varying representations Open
Comprehensive modeling of a whole cell requires an integration of vast amounts of information on various aspects of the cell and its parts. To divide-and-conquer this task, we introduce Bayesian metamodeling, a general approach to modeling…
View article: Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor
Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor Open
Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that exerts crucial metabolic functions by binding and activating its cognate receptor, GIPR. As an important therapeutic target, GIPR has been subjected to intensive …