The total average interaction energy (ΔE FMO ) (DA-QM-FMO) of a binding mode is obtained by calculating the average interaction energy ΔE FMO of all snapshots found per cluster divided by the number of snapshots within the cluster (MD frames) as shown in equation ( ). 40 ): (ΔE FMO ) DA-QM-FMO represents the average ΔE FMO per cluster; i and N denote the indices of the MD snapshots and the total number of MD snapshots per cluster, respectively.