{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Elisi GM"],"funding":["CINECA","Ministero dell&apos;Istruzione, dell&apos;Universit?? e della Ricerca"],"pagination":["210-222"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8757440"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["62(1)"],"pubmed_abstract":["The effects of the neurohormone melatonin are mediated by the activation of the GPCRs MT<sub>1</sub> and MT<sub>2</sub> in a variety of tissues. Crystal structures suggest ligand access to the orthosteric binding site of MT<sub>1</sub> and MT<sub>2</sub> receptors through a lateral channel between transmembrane (TM) helices IV and V. We investigated the feasibility of this lipophilic entry route for 2-iodomelatonin, a nonselective agonist with a slower dissociation rate from the MT<sub>2</sub> receptor, applying enhanced sampling simulations and free-energy calculations. 2-Iodomelatonin unbinding was investigated with steered molecular dynamics simulations which revealed different trajectories passing through the gap between TM helices IV and V for both receptors. For one of these unbindin"],"journal":["Journal of chemical information and modeling"],"pubmed_title":["Free-Energy Simulations Support a Lipophilic Binding Route for Melatonin Receptors."],"pmcid":["PMC8757440"],"funding_grant_id":["HP10CB3GC3","HP10CI4MQB","20175SA5JJ"],"pubmed_authors":["Rivara S","Lodola A","Scalvini L","Mor M","Elisi GM"],"additional_accession":[]},"is_claimable":false,"name":"Free-Energy Simulations Support a Lipophilic Binding Route for Melatonin Receptors.","description":"The effects of the neurohormone melatonin are mediated by the activation of the GPCRs MT<sub>1</sub> and MT<sub>2</sub> in a variety of tissues. Crystal structures suggest ligand access to the orthosteric binding site of MT<sub>1</sub> and MT<sub>2</sub> receptors through a lateral channel between transmembrane (TM) helices IV and V. We investigated the feasibility of this lipophilic entry route for 2-iodomelatonin, a nonselective agonist with a slower dissociation rate from the MT<sub>2</sub> receptor, applying enhanced sampling simulations and free-energy calculations. 2-Iodomelatonin unbinding was investigated with steered molecular dynamics simulations which revealed different trajectories passing through the gap between TM helices IV and V for both receptors. For one of these unbindin","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2026-05-09T05:58:45.288Z","creation":"2022-02-11T16:20:46.486Z"},"accession":"S-EPMC8757440","cross_references":{"pubmed":["34932329"],"doi":["10.1021/acs.jcim.1c01183"]}}