Scaffold hopping potential, virtual screening

A further important option for ligand-based virtual screening is to perform shape comparisons that have a pronounced scaffold hopping potential. An often used method of this kind is ROCS [31] (OpenEye Scientific Sofiware, 9 Bisbee Court Suite D, Santa Fe, NM 87508, USA. Available at http //www.eyesopen.com, March 20, 2009). ROCS employs continuous functions that are derived from atom-centered Gaussians to calculate the volume overlap between two 3D structures. The use of Gaussians drastically speeds up the computational process, and ROCS is able to search even databases with millions of compounds for molecules that can adopt shapes similar to the reference compound. As in the case of 3D pharmacophore searches, the low-energy conformations must be precomputed for the search database. 

The simplest way to compare the performance of different descriptors is to perform a retrospective study and to count the numbers of true actives found in different virtual screening hit lists of predefined size and compare them with the hit rate in the search database (enrichment). Enrichment factors, however, are not sufficient to assess the scaffold hopping potential of a descriptor or a search method. 

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