Substrate – Inositol Transporter Interactions: Molecular Docking Study
Inositol is a cyclic polyol naturally occurring as seven optically inactive stereoisomers and
one enantiomeric pair. Within the human body, brain is the most saturated organ of inositol, mainly
with myo- and scyllo-inositol. One of the molecular mechanisms for the maintenance of inositol brain
levels is active transport via stereospecific carrier molecules – one hydrogen myo-inositol transporter
(HMIT) and two sodium myo-inositol transporters (SMIT1 and SMIT2). In this study, we modeled by
homology the myo-inositol transporter SMIT1 using the X-ray structure of Vibrio parahaemolyticus
sodium/galactose symporter (vSGLT) as a template. A set of inositol derivatives – strong and weak
competitors of inositol transport – was docked in the SMIT1 binding site. The docking protocol was
optimized in terms of scoring function, radius of the binding site and flexible residues inside to distinguish
between strong and weak competitors. The analysis of ligand – transporter interactions revealed
that tiny structural differences exist between strong and weak competitors. Both groups have almost equal number of hydroxyl
groups but the strong competitors are able to form more hydrogen bonds with the transporter (5.07 vs. 4.53 per
molecule) and take part in less hydrophobic interactions (0.6 vs. 0.73) than the weak competitors.
Keywords: Inositol, SMIT1, docking, strong and weak competitors, hydrogen bonds, hydrophobic interactions.
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