We used MDM to search for a molecule with high atomization energy in (BF, CO)CS. The results are compared with our previous work 10 (Figure ). MDM started with BF and designed CO with higher atomization energy than BF. The atomization energy, participation coefficients representing the molecular species, and equilibrium bond length vary monotonically in the MDM procedure. The update of the molecular species accounts for the change in the equilibrium geometry in the optimization of the atomization energy (see Methods section). This design was also implemented in our previous study Ref. 10; the difference between this work and Ref. 10 is the algorithm for updating the molecular species. In Ref. 10, the constraints on the domain of definition for a (Eqs. ( ) and ( )) are removed by the variable transformation, and a are updated according to the steepest descent formula. However, the present MDM uses the optimality criteria method (Eq. ( )). Both the steepest descent and optimality criteria methods require a few parameters. In addition, the convergence conditions for are different. Nonetheless, we compared the design efficiencies. We obtained identical design results regardless of the optimization algorithm. On the other hand, there is an obvious difference in design efficiency.