Evidently, in the rugged energy landscape of NCI, reducing the energetics of the RMSD biasing is not sufficient to reliably find the lowest-energy conformers. In addition, a diversity of starting structures are required to reliably find better minima. Starting from a collection of known low-energy structures would intuitively be preferable to random or high-energy structures, as the low-energy structures can be presumed to be more similar to the global minimum. However, it was not immediately obvious how to select the starting structures.