Enhancing Automated Reaction Discovery with Boxed Molecular Dynamics in Energy Space

The rare event acceleration method “Boxed Molecular Dynamics in Energy space” (BXDE) is interfaced in the present work with the automated reaction discovery method AutoMeKin. To test the efficiency of the combined AutoMeKin‐BXDE procedure, the ozonolysis of α‐pinene is studied in comparison with standard AutoMeKin. AutoMeKin‐BXDE locates intermediates and transition states that are more densely connected with each other and approximately 50 kcal/mol more stable than those found with standard AutoMeKin. Other than the different density of edges between the nodes, both networks are scale‐free and display small‐world properties, mimicking the network of organic chemistry. Finally, while AutoMeKin‐BXDE finds more transition states than those previously reported for O3+α‐pinene, the standard procedure fails to locate some of the previously published reaction pathways using the same simulation time of 2.5 ns. In summary, the mixed procedure is very promising and clearly outperforms the standard simulation algorithms implemented in AutoMeKin. BXDE will be available in the next release of AutoMekin. Inside the box: The efficiency of the molecular dynamics based reaction discovery method, AutoMekin, is significantly improved by interfacing it with boxed molecular dynamics in energy space (BXDE). AutoMeKin‐BXDE creates more densely connected networks and more reliable reaction mechanisms.