Free-energy analysis of lysozyme-triNAG binding modes with all-atom molecular dynamics simulation combined with the solution theory in the energy representation

► Binding free energy calculation method for protein-ligand complex is proposed. ► Calculation is conducted with the solution theory in the energy representation. ► Four distinct lysozyme-triNAG binding modes are examined. ► Crystal binding mode is identified as the lowest binding energy mode. ► We conclude that the method can be used to distinguish more plausible binding mode.