A5023803281- Biochemical Analysis and Sensing Techniques
- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Ion channel regulation and function
- Advanced Chemical Sensor Technologies
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Synthesis and Biological Evaluation
- Cellular transport and secretion
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Advanced biosensing and bioanalysis techniques
- Computational Drug Discovery Methods
University of North Carolina at Chapel Hill
2023-2024
Pohang University of Science and Technology
2020-2022
AlphaFold2 (AF2) models have had wide impact but mixed success in retrospective ligand recognition. We prospectively docked large libraries against unrefined AF2 of the σ
Abstract AlphaFold2 (AF2) and RosettaFold have greatly expanded the number of structures available for structure-based ligand discovery, even though retrospective studies cast doubt on their direct usefulness that goal. Here, we tested unrefined AF2 models prospectively , comparing experimental hit-rates affinities from large library docking against vs same screens targeting receptors. In σ 2 5-HT2A receptors, struggled to recapitulate ligands had previously found receptors’ structures,...
GPR158, a class C orphan GPCR, functions in cognition, stress-induced mood control, and synaptic development. Among GPCRs, GPR158 is unique as it lacks Venus flytrap-fold ligand-binding domain terminates Gαi/o protein signaling through the RGS7-Gβ5 heterodimer. Here, we report cryo-EM structures of alone complex with one or two heterodimers. dimerizes Per-Arnt-Sim-fold extracellular transmembrane (TM) domains connected by an epidermal growth factor-like linker. The TM (TMD) reflects both...
Abstract Activation of insulin receptor (IR) initiates a cascade conformational changes and autophosphorylation events. Herein, we determined three structures IR trapped by aptamers using cryo-electron microscopy. The A62 agonist aptamer selectively activates metabolic signaling. In the absence insulin, two agonists adopt an insulin-accessible arrowhead conformation mimicking site-1/site-2’ coordination. Insulin binding at one site triggers in protomer, but this movement is blocked other...