Microsecond-timescale simulations suggest 5-HT-mediated preactivation of the 5-HT_3A serotonin receptor.

ABSTRACT: Aided by efforts to improve their speed and efficiency, molecular dynamics (MD) simulations provide an increasingly powerful tool to study the structure-function relationship of pentameric ligand-gated ion channels (pLGICs). However, accurate reporting of the channel state and observation of allosteric regulation by agonist binding with MD remains difficult due to the timescales necessary to equilibrate pLGICs from their artificial and crystalized conformation to a more native, membrane-bound conformation in silico. Here, we perform multiple all-atom MD simulations of the homomeric 5-hydroxytryptamine 3A (5-HT_3A) serotonin receptor for 15 to 20 μs to demonstrate that such timescales are critical to observe the equilibration of a pLGIC from its crystalized conformation to a membr

SUBMITTER: Guros NB 

PROVIDER: S-EPMC6955379 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature