Journal of molecular graphics & modelling
August 1, 2008
Jenelle K Bray, William A Goddard
35 citations
Using computational methods, the three-dimensional structure of the serotonin 5-HT(2C) receptor was predicted, and the binding of several ligands—including serotonin, ritanserin, metergoline, and methiothepin—was modeled. The predicted structures for psilocybin analogs, both agonists and antagonists, matched known experimental data. Molecular dynamics simulations showed that the serotonin-bound receptor and binding site remained stable after 5 nanoseconds. The predicted 5-HT(2C) structure was deemed accurate enough for drug design. A comparison with a preliminary 5-HT(2B) receptor model revealed a structural difference in transmembrane helix 5, leading to distinct serotonin binding modes between the two receptors.
Journal of molecular graphics & modelling
November 1, 2016
Xiaomeng Xu, Shifan Ma, Zhiwei Feng et al.
19 citations
A new chemogenomics database specific to hallucinogens was built by collecting related chemicals, protein targets, and pathways. Combined with computational tools TargetHunter and HTDocking, it offers a one-step platform for studying hallucinogen mechanisms. Using salvinorin A from Salvia divinorum as a test case, HTDocking predicted four novel targets: muscarinic acetylcholine receptor 2, cannabinoid receptors 1 and 2, and dopamine receptor 2. Binding modes, poses, and docking scores suggest salvinorin A may interact with some of these targets. The database enriches systems pharmacology analysis, target identification, and drug discovery for hallucinogens, addressing the lack of a dedicated resource for mechanism research.
Journal of molecular graphics & modelling
April 1, 2010
Donna L Mcgovern, Philip D Mosier, Bryan L Roth et al.
16 citations
A key insight reveals why particular Salvinorin A derivatives bind more effectively to specific brain receptors: their precise molecular shape matters. Scientists employed computational modeling to develop highly predictive models, showing how subtle structural changes at a crucial C-2 position influence binding. The findings pinpoint a specific binding mechanism for amine-containing versions, explaining why one molecular orientation (beta-epimers) consistently achieves stronger binding than another. This offers valuable insights for designing compounds with tailored receptor interactions.