Computation-guided analysis of paroxetine binding to hSERT reveals functionally important structural elements and dynamics.

ABSTRACT: The serotonin transporter (SERT) is one of the primary targets for medications to treat neuropsychiatric disorders and functions by exploiting pre-existing ion gradients of Na⁺, Cl^-, and K⁺ to translocate serotonin from the synaptic cleft into the presynaptic neuron. Although recent hSERT crystal structures represent a milestone for structure-function analyses of mammalian neurotransmitter:sodium symporters, they are all derived from thermostabilized but transport-deficient constructs. Two of these structures are in complex with paroxetine, the most potent selective serotonin reuptake inhibitor known. In this study, by carrying out and analyzing the results of extensive and comparative molecular dynamics simulations while also re-evaluating the transport an

SUBMITTER: Abramyan AM 

PROVIDER: S-EPMC6494725 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature