CHEMICAL DESCRIPTION OF THE INTERACTION BETWEEN GLYCAN LIGAND AND SIGLEC-7 USING AB INITIO FMO METHOD AND CLASSICAL MD SIMULATION

Abstract

We clarified in detail the theoretical features of the interaction between the glycan ligand containing α(2,8)-disialyl residue and a lectin called Siglec (sialic acid Ig-like binding lectin)-7 by ab initio fragment molecular orbital (FMO) calculations and classical molecular dynamics (MD) simulations. By comparing the ligand–Siglec-7 interaction of the wild-type Siglec-7 and those of mutant-Siglec-7s, we herein describe protein–glycan interactions thoroughly, and provide fundamentals to elucidate ligand-recognition mechanism. The experimentally observed decrease in ligand binding produced by mutagenesis at residues in non-active site was explained with MD simulations; both Trp85 and Trp74 residues are fundamental in structural stability of the Siglec-7, which is involved in the binding of the glycan ligand. The interaction energies obtained by the FMO method were consistent with the experimental ligand-binding results. The glycan ligand preferentially interacted with Siglec-7 via sialic acid residues. The stabilization by the dispersion interaction between the neutral parts of the ligand was also considerable in the binding.