Development of Refined Homology Models: Adding the Missing Information to the Medically Relevant Neurotransmitter Transporters

摘要: Neurotransmitter:sodium symporters are located on presynaptic neurons and terminate neurotransmission by removing the monoamine substrates from synaptic cleft. Until very recently, only several conformational snapshots/structures of a bacterial homolog neurotransmitter:sodium symporters, namely, leucine/alanine transporter LeuT Aquifex aeolicus, were available. However, this shares 21b % overall sequence identity with its human homologs. In chapter, we describe how model can be developed template such low identity. The effort building will strongly depend purpose. We discuss process focus important steps that allowed us to obtain which used for molecular dynamics simulations. Furthermore, also highlight inherent limitations proposed approaches. Prediction ligand binding brings in additional complexity. Therefore, experimental scrutiny resulting models is key component successful validation. two specific examples: dopamine docking serotonin transporter. evaluate our modeling approach direct comparison recently published first eukaryotic symporter, drosophila melanogaster DAT