We discuss the coordination mechanism of Fe III and methyl-a-mannopyranoside in aqueous solution using a recently presented integrated approach comprising ab initio electronic structure calculations, molecular dynamics simulations, and mass spectrometric measurements. First principles Car-Parrinello molecular dynamics (CPMD) simulations find that a single Fe III ion interacts with specific hydroxyl groups of the saccharide in aqueous solution. Specifically, we find that one Fe III ion complexed to methyl-α-mannopyranoside also associates with two water molecules. These simulations are in accord with electrospray ionization mass spectrometry measurements involving guided ion beam hydration measurements, which reveal an optimal coordination number of four about the Fe III ion. CPMD simulations identified specific intramolecular and intermolecular hydrogen bonding interactions that have an impact on the conformation of the saccharide and on the coordination with Fe III; in contrast, classical molecular dynamics simulations were insensitive to these effects. This study illustrates the strength of ab initio molecular dynamics simulations, chemical reactivity calculations, and natural partial charge analysis coupled with mass spectrometric measurements in identifying the active sites of biomolecules toward ligands and for studying the complexation and coordination chemistry associated with substrate and ligand interactions relevant to the design of biochemical syntheses, drugs, and biomarkers in medicine.