Molecular dynamics simulations of Na+/Cl(-)-dependent neurotransmitter transporters in a membrane-aqueous system |
| |
Authors: | Jørgensen Anne Marie Tagmose Lena Jørgensen Anne Marie M Bøgesø Klaus P Peters Günther H |
| |
Affiliation: | MEMPHYS-Center for Biomembrane Physics, Department of Chemistry, Technical University of Denmark, Building 206, 2800 Kgs. Lyngby, Denmark. |
| |
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 5-HT or the selective serotonin reuptake inhibitor escitalopram. 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 crystallographic 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 escitalopram. 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-escitalopram complexes. Our findings are in good agreement with predictions from mutagenesis studies. |
| |
Keywords: | escitalopram induced fit molecular dynamics molecular recognition neurotransmitter transporters |
本文献已被 PubMed 等数据库收录! |
|