When forming a binary complex between two proteins, the binding free energy between individual proteins is the free-energy difference between the binary complex (R AB ) and unbound proteins (R A and R B ). If there exists a predominant bound-state geometry R * AB , of which the partition function dominates the entire bound-state ensemble, the binding free energy can be approximated as the free-energy difference between unbound state and dominant bound state (depicted on the two ends of Figure ),