Fig. 5: MD simulations of possible VLZ binding poses.
From: The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter
Zoomed view of VLZ modeled into the allosteric binding site of SERT. Parts of SERT TMs and bound IMI are removed for clarity. a The refined cryo-EM SERT structure (blue ribbons) with VLZ (magenta) superimposed onto the final MD simulated SERT structure (orange ribbons) with VLZ (orange) in the hypothezised pose. b Structure of the refined SERT:VLZ complex modeled with the 180° flipped VLZ in its binding site and superimposed onto the final MD simulated SERT structure (gray ribbons) with VLZ (gray) in the flipped pose. The MD simulations-derived structures of (c) SERT with VLZ bound at the hypothesized pose and (d) the flipped pose, both superimposed on the VLZ electron density from the cryo-EM structure. e, f As in c and d, viewed from the plane of the membrane, showing that the indole ring in the hypothesized pose could explain the density feature in the cryo-EM structure. TM: Transmembrane.
