If  > 0, cooperativity is positive, indicating that adding an additional building block into the system will induce stronger interactions among the components. If  < 0, cooperativity is negative, meaning that adding an extra piece of the building block will lead to a smaller interaction energy. The scenario of  = 0 means no cooperativity. As illustrated by six examples in Fig. , we unveil that homogeneous complexes are positively cooperative, but charged ones are negatively cooperative. To quantify frustration, as elucidated in Fig. , we introduced a new reference state, where all individual species assume the same geometry as the complex in the most stable state. The total energy difference between the individuals in the isolated state and this new reference state is the energetic sacrifice paid by the individuals. As exhibited by Fig. , we demonstrated that frustration can be both positive and negative as well, but its magnitude is less than that of cooperation. Also, we found that for small molecular clusters, there exists no minimum frustration principle. As illustrated in Fig. , when the conformation space of a molecular complex is sampled, frustration can be either small or large, depending on the nature of the complex.