Sketcher in Maestro (version 2017-4) (Schrodinger Inc., U.S.A.) and each structure was ionized completely, that is COO -, NH3 + and P-O -. The 3D structures were built and saved as 3D project entries by using 2D Sketcher. These 3D structures were submitted to System Builder Panel to be charge-neutralized by adding a single Na + atom. Then, each molecule was embedded in a 10Å x 10Å x 10Å water (TIP3P) solvent box and the system was buffered with 0.15 M NaCl with using the OPLS3 force field. The whole system (molecule + Na + + water + NaCl) was relaxed by a simple molecular dynamics calculation with Desmond (version 2017-4) (Schrodinger Inc., U.S.A.) for 5 nsec using the OPLS3 force field at 300K. The structure after 5 nsec relaxation was used as the initial structure for the following replica exchange calculations and metadynamics calculations.