5-HT<sub>2</sub> Receptor Subfamily and the Halogen Bond Promise
| dc.contributor.author | Fierro, Angelica | |
| dc.contributor.author | Matthies, Douglas J. | |
| dc.contributor.author | Cassels, Bruce K. | |
| dc.contributor.author | Jaque, Pablo | |
| dc.contributor.author | Zapata-Torres, Gerald | |
| dc.date.accessioned | 2025-01-20T22:06:05Z | |
| dc.date.available | 2025-01-20T22:06:05Z | |
| dc.date.issued | 2021 | |
| dc.description.abstract | The binding of C-4-halogenated 1-(4-X-2,5-dimethoxyphenyl)-2-aminopropane (DOX) serotonin agonist psychedelics at all three 5-HT2 receptor subtypes is up to two orders of magnitude stronger for X = Cl, Br, or I (but not F) than when C-4 bears a hydrogen atom and more than expected from their hydrophobicities. Our docking and molecular dynamics simulations agree with the fact that increasing the polarizability of halogens results in halogen-oxygen distances to specific backbone C=O groups, and C-X center dot center dot center dot O angles, in ranges expected for halogen bonds (XBs), which could contribute to the high affinities observed. Good linear correlations are found for each receptor type, indicating that the binding pocketl-igand affinity is enhanced as the XB interaction becomes stronger (i.e., I approximate to Br > Cl > F). It is also striking to note how the linear equations unveil that the receptor's response on the strength of the XB interaction is quite similar among 5-HT2A and 5-HT2C, whereas the 5-HT2B's sensitivity is less. The calculated dipole polarizabilities in the binding pocket of the receptors reflect the experimental affinity values, indicating that less-polarizable and harder binding sites are more prone to XB formation. | |
| dc.description.funder | Comision Nacional Cientifica y Tecnologica CONICYT (Chile) through FONDECYT | |
| dc.fuente.origen | WOS | |
| dc.identifier.doi | 10.1021/acs.jcim.1c00466 | |
| dc.identifier.eissn | 1549-960X | |
| dc.identifier.issn | 1549-9596 | |
| dc.identifier.uri | https://doi.org/10.1021/acs.jcim.1c00466 | |
| dc.identifier.uri | https://repositorio.uc.cl/handle/11534/94187 | |
| dc.identifier.wosid | WOS:000711200000017 | |
| dc.issue.numero | 10 | |
| dc.language.iso | en | |
| dc.pagina.final | 5012 | |
| dc.pagina.inicio | 5001 | |
| dc.revista | Journal of chemical information and modeling | |
| dc.rights | acceso restringido | |
| dc.title | 5-HT<sub>2</sub> Receptor Subfamily and the Halogen Bond Promise | |
| dc.type | artículo | |
| dc.volumen | 61 | |
| sipa.index | WOS | |
| sipa.trazabilidad | WOS;2025-01-12 |