A5060143660- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Nicotinic Acetylcholine Receptors Study
- Photoreceptor and optogenetics research
- Chemical Synthesis and Analysis
- Lipid Membrane Structure and Behavior
- Mass Spectrometry Techniques and Applications
- Molecular Sensors and Ion Detection
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Psychedelics and Drug Studies
- Neurobiology and Insect Physiology Research
- Molecular Junctions and Nanostructures
- Neural dynamics and brain function
- Advanced biosensing and bioanalysis techniques
- Biochemical and Structural Characterization
- Neurotransmitter Receptor Influence on Behavior
- Electrochemical Analysis and Applications
- Chemical synthesis and alkaloids
- Enzyme Structure and Function
- Pancreatic function and diabetes
- Biochemical Analysis and Sensing Techniques
- Spectroscopy and Quantum Chemical Studies
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
Stanford University
2021-2022
University of Oxford
2017-2021
Biomolecular simulation is increasingly central to understanding and designing biological molecules their interactions. Detailed, physics‐based methods are demonstrating rapidly growing impact in areas as diverse biocatalysis, drug delivery, biomaterials, biotechnology, design. Simulations offer the potential of uniquely detailed, atomic‐level insight into mechanisms, dynamics, processes, well accurate predictions molecular properties. can now be used computational assays activity, for...
Pentameric ligand-gated ion channels are key players in mediating fast neurotransmission. Glycine receptors chloride-selective members of this receptor family that mediate inhibitory synaptic transmission and implicated neurological disorders including autism hyperekplexia. They have been structurally characterized by both X-ray crystallography cryoelectron microscopy (cryo-EM) studies, with the latter giving rise to what was proposed as a possible open state. However, recent work has...
Pentameric ligand-gated ion channels (pLGICs) are receptor proteins that sensitive to their membrane environment, but the mechanism for how lipids modulate function under physiological conditions in a state dependent manner is not known. The glycine pLGIC whose structure has been resolved different functional states. Using realistic model of neuronal coupled with coarse-grained molecular dynamics simulations, we demonstrate some key lipid-protein interactions on state, suggesting may...
Glycine receptors (GlyR) belong to the pentameric ligand-gated ion channel (pLGIC) superfamily and mediate fast inhibitory transmission in vertebrate CNS. Disruption of glycinergic by inherited mutations produces startle disease man. Many are GlyRs provide useful clues function domains. E103K is one few found extracellular agonist binding site channel, loop A principal side subunit interface. Homology modeling shows that chain Glu-103 close Arg-131, E complementary site, may form a salt...
Serotonin (5-hydroxytryptamine; 5-HT) 5-HT2-family receptors represent essential targets for the prototypical psychedelic LSD and all other drugs. Although canonical signaling pathway 5-HT2 is mediated by Gq protein activation, pathways β-arrestin recruitment appear actions of in vitro vivo. To gain comprehensive molecular insights into mechanisms LSD, we determined cryoEM structures LSD-bound 5-HT2BR transducer-free, protein-coupled β-arrestin-1-coupled states. These provide distinct...
Abstract Pentameric ligand-gated ion channels (pLGICs) are receptor proteins that sensitive to their membrane environment, but the mechanism for how lipids modulate function under physiological conditions in a state dependent manner is not known. The glycine pLGIC whose structure has been resolved different functional states. Using realistic model of neuronal coupled with coarse-grained molecular dynamics simulations, we demonstrate lipid-protein interactions on state, suggesting may...
Abstract Fast neurotransmission is mediated by pentameric ligand-gated ion channels. Glycine receptors are chloride-selective members of this receptor family that mediate inhibitory synaptic transmission and implicated in neurological disorders including autism hyperekplexia. They have been structurally characterized both X-ray crystallography cryo electron microscopy studies, with the latter giving rise to what was proposed as a possible open state. However, recent work has questioned...
Abstract The neuropeptide Substance P (SP) is important in pain and inflammation. SP activates the neurokinin-1 receptor (NK1R) to signal via G q s proteins. Neurokinin A also NK1R, but leads selective signaling. How two stimuli yield distinct G-protein signaling at same G-protein-coupled-receptor remains unclear. We determined cryo-EM structures of active NK1R bound or -biased peptide SP6-11. Peptide interactions deep within are critical for activation. Conversely, between extracellular...