title: Identification of active sites of biomolecules II: Saccharide and transition metal ion in aqueous solution.
abstract: We discuss the coordination mechanism of Fe(III) and methyl-alpha-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-alpha-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.
authors.affiliation: Computational Chemistry Group, Physical and Chemical Properties Division, National Institute of Standards and Technology, 100 Bureau Drive, Mail Stop 8380, Gaithersburg, Maryland 20899, USA. orkid.coskuner@nist.gov
authors.forename: Orkid
authors.initials: O
authors.lastname: Coskuner
authors.forename: Denis E
authors.initials: DE
authors.lastname: Bergeron
authors.forename: Luis
authors.initials: L
authors.lastname: Rincon
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Hudgens
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Gonzalez
mesh_terms: D020134:Catalytic Domain; D007477:Ions; D007501:Iron; D008766:Methylmannosides; D009005:Monosaccharides / Q000737:chemistry*; D012996:Solutions; D028561:Transition Elements / Q000737:chemistry*
chemical_list: D007477:Ions; D008766:Methylmannosides; D009005:Monosaccharides; D012996:Solutions; D028561:Transition Elements; D007501:Iron