Molecular dynamics simulations of Na+/Cl--dependent neurotransmitter transporters in a membrane-aqueous system

Anne Marie Jørgensen, L. Tagmose, A.M.M. Jørgensen, K.P. Bogeso, Günther H.j. Peters

Research output: Contribution to journalJournal articleResearchpeer-review


We have performed molecular dynamics simulations of a homology model of the human serotonin transporter (hSERT) in a membrane environment and in complex with either the natural substrate S-HT or the selective serotonin reuptake inhibitor escitaloprom. We have also included a transporter homologue, the Aquifex aeolicus leucine transporter (LeuT), in our study to evaluate the applicability of a simple and computationally attractive membrane system. Fluctuations in LeuT extracted from simulations are in good agreement with crystal logrophic B factors. Furthermore, key interactions identified in the X-ray structure of, LeuT are maintained throughout the simulations indicating that our simple membrane system is suitable for studying the transmembrane protein hSERT in complex with 5-HT or escitoloprom. For these transporter complexes, only relatively small fluctuations are observed in the ligand-binding cleft. Specific interactions responsible for ligand recognition, are identified in the hSERT-5HT and hSERT-escitaloprom complexes. Our finding5 are in good agreement with predictions from mutagenesis studies.
Original languageEnglish
Issue number6
Pages (from-to)827-840
Number of pages14
Publication statusPublished - 2007


  • Escitalopram
  • Induced fit
  • Molecular dynamics
  • Molecular recognition
  • Neurotransmitter transporters


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