Unbiased picture of the ligand docking process for the hevein protein–oligosaccharide complex

The ligand-docking behavior of hevein, the major latex protein from the rubber tree Hevea brasiliensis (Euphorbiaceae), has been investigated by the unguided molecular dynamics (MD) simulation method. An oligosaccharide molecule, initially placed in an arbitrary position, was allowed to move around hevein for a prolonged simulation time, on the order of microseconds, with the expectation of spontaneous ligand docking of the oligosaccharide molecule to the binding site of hevein. In the binary solution system consisting of a hevein molecule and a chito-trisaccharide (GlcNAc₃) molecule, three out of the six separate simulation runs successfully reproduced the complex structure of the observed binding from. It appeared that the surface topology formed by two aromatic side chains of the hevein molecule played a role in orienting the GlcNAc₃ molecule in the correct direction. We also performed MD simulations of the ternary solution system containing a cello-hexasaccharide (Glc₆) molecule in addition to hevein and a chito-hexasaccharide (GlcNAc₆) molecule. Formation of hevein-GlcNAc₆ complex structures was exclusively observed, while the Glc₆ molecule remained in the solvent phase throughout the simulations. Obviously, the acetamide groups of GlcNAc play a role in detecting the binding site and its vicinity on the protein surface.