Dimer Interface of the Human Serotonin Transporter and Effect of the Membrane Composition.

ABSTRACT: The oligomeric state of membrane proteins has recently emerged in many cases as having an effect on their function. However, the intrinsic dynamics of their spatial organization in cells and model systems makes it challenging to characterize. Here we use molecular dynamics (MD) simulations at multiple resolutions to determine the dimer conformation of the human serotonin transporter (hSERT). From self-assembly simulations we predict dimer candidates and subsequently quantify their relative strength. We use umbrella sampling (US) replica exchange MD simulations for which we present extensive analysis of their efficiency and improved sampling compared to regular US MD simulations. The data shows that the most stable hSERT dimer interface is symmetrical and involves transmembrane helix 12 (TM

SUBMITTER: Periole X 

PROVIDER: S-EPMC5865177 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature