Journal article
Molecular dynamics simulations of Na+/Cl--dependent neurotransmitter transporters in a membrane-aqueous system
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.
Language: | English |
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Publisher: | WILEY-VCH Verlag |
Year: | 2007 |
Pages: | 827-840 |
ISSN: | 18607187 and 18607179 |
Types: | Journal article |
DOI: | 10.1002/cmdc.200600243 |
ORCIDs: | Peters, Günther H.j. |
Escitalopram Induced fit Molecular dynamics Molecular recognition Neurotransmitter transporters
Bacterial Proteins Binding Sites Citalopram Computer Simulation Humans Leucine Models, Molecular Protein Binding Protein Interaction Mapping Selective Serotonin Reuptake Inhibitors Serotonin Serotonin Plasma Membrane Transport Proteins Serotonin Uptake Inhibitors Sodium Chloride Solvents Thermodynamics Water