The structure of human serotonin 2c G-protein-coupled receptor bound to agonists and antagonists.
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.