100 iterations are required to reach the same optimization criteria as in the default settings of the ORCA program. The RMSD between both final structures is 0.04 Å, and with more iterations used in the NN optimization (300), the RMSD improvement is already negligible (lowered to 0.03 Å). When taking the NN-optimized structure, less than an extra 2 CPUhours were required for B97-3c optimization to reach the minimum structure, which differs from the fully QC-optimized structure by ∼0.01 Å in RMSD (considered as the same geometry). Although there is already a 10-fold speed-up in a single optimization, there will be a massive overall speed-up by omitting numerous energetically high-lying configurations after the NN pre-optimization. This clearly underlines that NN techniques will play an important role in future studies of large molecular clusters.