Hello, 
 I am trying to calculate binding energy for a set of poses generated by flexible docking algorithm in addition to ligand conformational entropy. 

Energy_Binding = Energy_Complex - Energy_Ligand - Energy_Receptor

Intuitively, the ligand with most negative binding energy is the one with the tightest binding. However the results seems to contradict our findings using CDOCKER, LIBDOCK, Flexible Docking. Isn't the most negative ligand the tightest to bind ? 

Discovery studio 2016 , Tools>Dock ligands> Scoring> Calculate binding energy.