Force‐field parameters of the Ψ and Φ around glycosidic bonds to oxygen and sulfur atoms

The Ψ and Φ torsion angles around glycosidic bonds in a glycoside chain are the most important determinants of the conformation of a glycoside chain. We determined force‐field parameters for Ψ and Φ torsion angles around a glycosidic bond bridged by a sulfur atom, as well as a bond bridged by an oxygen atom as a preparation for the next study, i.e., molecular dynamics free energy calculations for protein‐sugar and protein‐inhibitor complexes. First, we extracted the Ψ or Φ torsion energy component from a quantum mechanics (QM) total energy by subtracting all the molecular mechanics (MM) force‐field components except for the Ψ or Φ torsion angle. The Ψ and Φ energy components extracted (hereafter called “the remaining energy components”) were calculated for simple sugar models and plotted as functions of the Ψ and Φ angles. The remaining energy component curves of Ψ and Φ were well represented by the torsion force‐field functions consisting of four and three cosine functions, respectively. To confirm the reliability of the force‐field parameters and to confirm its compatibility with other force‐fields, we calculated adiabatic potential curves as functions of Ψ and Φ for the model glycosides by adopting the Ψ and Φ force‐field parameters obtained and by energetically optimizing other degrees of freedom. The MM potential energy curves obtained for Ψ and Φ well represented the QM adiabatic curves and also these curves' differences with regard to the glycosidic oxygen and sulfur atoms. Our Ψ and Φ force‐fields of glycosidic oxygen gave MM potential energy curves that more closely represented the respective QM curves than did those of the recently developed GLYCAM force‐field. © 2009 Wiley Periodicals, Inc., J Comput Chem, 2009