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

We propose a method for calculating the binding free energy of protein-ligand complexes using all-atom molecular dynamics simulation combined with the solution theory in the energy representation. Four distinct modes for the binding of tri-N-acetyl-d-glucosamine (triNAG) to hen egg-white lysozyme were investigated, one from the crystal structure and three generated by docking predictions. The proposed method was demonstrated to be used to distinguish the most plausible binding mode (crystal model) as the lowest binding energy mode.