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Real-Time Shape Similarity for Virtual Screening, Lead Hopping & Shape Clustering

BioIT Best of Show WinnerFastROCS 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 [1], so it is possible to routinely minimize to the best global match.

The unprecedented speed of FastROCS represents a paradigm shift in the potential for 3D shape screening as part of the drug discovery process. Now, in just seconds, FastROCS 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 [2]). Recent work suggests that the underlying ligand-based shape similarity approach is competitive with, and often superior to, structure-based approaches in virtual screening [3,4], both in terms of overall performance and consistency [5].

In addition to revolutionizing the capabilities of virtual screening and lead hopping, FastROCS opens the door to performing NxN shape comparisons over an entire multiconformer database. This ability makes 3D shape clustering of large databases a practical possibility for the first time.

FastROCS alignments have a number of additional applications including: 3D QSAR, SAR analysis, understanding of scaffold diversity and detection of common binding elements. Alignments to crystallographic conformations have also been useful in pose prediction in the absence of a protein structure [6].


FastROCS GPU comparison chart

FastROCS continues to show dramatic increases in performance with every new generation of NVidia GPU.



Two molecules with substantially different chemistry from the query (green), but high shape similarity (T shape >0.75).



  • Processes millions of conformations per second
  • Returns overlays based on the quality of the 3D shape match against the query
  • Overlays are intuitive and visually informative when viewed in standard visualizers (e.g. VIDA)
  • Available as an XML-RPC based web service
  • Jobs can be launched and the subsequent results viewed directly from within VIDA
  • Reports rigorous Tanimoto measure between shapes


  1. A fast method of molecular shape comparison: A simple application of a Gaussian description of molecular shape Grant, J.A., Gallardo, M.A., Pickup, B., J. Comp. Chem., 1996, 17, 1653.
  2. A shape-based 3-D scaffold hopping method and its application to a bacterial protein-protein interaction Rush, T.S., Grant, J.A., Mosyak, L., Nicholls, A., J. Med. Chem., 2005, 48, 1489.
  3. Comparison of Shape-Matching and Docking as Virtual Screening Tools Hawkins, P.C.D., Skillman, A.G., Nicholls, A., J. Med. Chem., 2007, 50, 74.
  4. Assessment of Scaffold Hopping Efficiency by Use of Molecular Interaction Fingerprints Venhorst, J., Nunez, S., Terpstra, J.W., Kruse, C.G., J. Med. Chem., 2008, 51, 3222.
  5. Multiple protein structures and multiple ligands: effects on the apparent goodness of virtual screening results Sheridan, R.P., McGaughey, G.B., Cornell, W.D., J. Comput. Aided Mol. Des., 2008, 22, 257.
  6. Lessons in molecular recognition. 2. Assessing and improving cross-docking accuracy Sutherland, J.J., Nandigam, R.K., Erickson, J.A., Vieth, M. J. Chem., Inf. Model, 2007, 47, 2293.