Abstract
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.
Graphical Abstract
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