Abstract
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 language | English |
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Journal | ChemMedChem |
Volume | 2 |
Issue number | 6 |
Pages (from-to) | 827-840 |
Number of pages | 14 |
ISSN | 1860-7179 |
DOIs | |
Publication status | Published - 2007 |
Keywords
- Escitalopram
- Induced fit
- Molecular dynamics
- Molecular recognition
- Neurotransmitter transporters