Neuron
July 15, 2025
Manish K. Jain, Ryan H. Gumpper, Samuel T. Slocum et al.
42 citations
The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT2A serotonin receptor (5-HT2AR). Recent clinical studies have suggested that classical psychedelics may additionally have therapeutic potential for many neuropsychiatric conditions including depression, anxiety, migraine and cluster headaches, drug...
Nature Communications
March 19, 2025
Ryan H. Gumpper, Manish K. Jain, Kuglae Kim et al.
31 citations
There is currently a resurgence in exploring the utility of classical psychedelics to treat depression, addiction, anxiety disorders, cluster headaches, and many other neuropsychiatric disorders. A biological target of these compounds, and a hypothesized target for their therapeutic actions, is the 5-HT2A serotonin receptor. Here, we present 7 cryo-EM structures covering all major compound...
Science
May 16, 2024
Jiankun Lyu, Nicholas J. Kapolka, Ryan H. Gumpper et al.
145 citations
AlphaFold2 (AF2) models have had wide impact but mixed success in retrospective ligand recognition. We prospectively docked large libraries against unrefined AF2 models of the σ 2 and serotonin 2A (5-HT2A) receptors, testing hundreds of new molecules and comparing results with those obtained from docking against the experimental structures. Hit rates were high and similar for the experimental...
Neuron
October 5, 2022
Can Cao, Ximena Barros-Álvarez, Shicheng Zhang et al.
158 citations
Serotonin (5-hydroxytryptamine [5-HT]) 5-HT2-family receptors represent essential targets for lysergic acid diethylamide (LSD) and all other psychedelic drugs. Although the primary psychedelic drug effects are mediated by the 5-HT2A serotonin receptor (HTR2A), the 5-HT2B serotonin receptor (HTR2B) has been used as a model receptor to study the activation mechanisms of psychedelic drugs due to...
Nature
September 28, 2022
Anat Levit Kaplan, Danielle N. Confair, Kuglae Kim et al.
There is considerable interest in screening ultralarge chemical libraries for ligand discovery, both empirically and computationally 1 – 4 . Efforts have focused on readily synthesizable molecules, inevitably leaving many chemotypes unexplored. Here we investigate structure-based docking of a bespoke virtual library of tetrahydropyridines—a scaffold that is poorly sampled by a general...