FastROCS TK is an extremely fast shape comparison application, based on the idea that molecules have similar shape if their volumes overlay well and any volume mismatch is a measure of dissimilarity. It uses a smooth Gaussian function to represent the molecular volume [Grant-1996], so it is possible to routinely minimize to the best global match. FastROCS will perform millions of these global shape matches every second. See the Molecular Shape section in the Shape TK theory documentation for a description of the shape and color theory used in FastROCS TK.
Now, in just seconds, FastROCS TK can perform a virtual screen over an entire multi-conformer representation of a corporate collection to find active compounds with similar shape to a lead compound (a task that could previously take up to a day [Rush-2005]). Recent work suggests that the underlying ligand-based shape similarity approach is competitive with, and often superior to, structure-based approaches in virtual screening [Hawkins-2007] [Venhorst-2008], both in terms of overall performance and consistency [Sheridan-2008]. Alignments to crystallographic conformations have also been useful in pose prediction in the absence of a protein structure [Sutherland-2007].
In addition to virtual screening and lead hopping, FastROCS TK can be used to perform NxN shape comparisons over an entire multiconformer database. A prototype of clustering with FastROCS TK can be found in the SphereExclusionClustering.py example program.