ROCS is a shape comparison program, based on the idea that molecules have similar shape if their volumes overlay well and any volume mismatch is a measure of dissimilarity. ROCS uses a smooth Gaussian function to represent the molecular volume [1], so it is possible to routinely minimize to the best global match. ROCS is capable of processing 600-800 comparisons each second, making it is possible to search multi-conformer representations of corporate collections in a day on a single processor to find compounds with similar shape to a lead compound.

Scientists at Wyeth Research credit the software with "allowing us to 'scaffold hop' to molecules without the same toxicity and potential intellectual property issues as the query."[2] ROCS screens of corporate databases have also successfully rescued hits missed by HTS, generated alignments for QSAR models, provided framework diversity analysis, and driven SAR analyses.

Two molecules with substantially different chemistry from the query (green), but high shape similarity (T_shape > 0.75). Select image to enlarge.

The primary features of ROCS include:

• Provides intuitive measure of similarity ("looks right")
• Reports rigorous Tanimoto and Tversky measure between shapes
• Allows smooth workflow with EON
• Output easily browsed in VIDA
• Matches to optional, user-definable chemical force-field
• Minimizes against shape and weighted chemical force-field
• Query shape may be a molecule, a grid (e.g. electron density, active site, or arbitrary volume) or a composite of the two
• OEChemplete - all I/O and molecular information processing by OEChem
• Robust reading and specification-compliant writing of SDF, MOL, MOL2, PDB, MacroModel, XYZ, CCP4, XPLOR and OEBinary file formats
• Support for LINUX, IRIX, Windows, OS X, AIX, HP-UX, Solaris, Tru64UNIX
• Support for 64-bit processing on IRIX, Itanium®2 Linux, PowerPC Linux, AIX, HP-UX, Tru64UNIX
• Distributed processing via PVM for most Unix platforms

[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.

Additional References:

"Comparison of Shape-Matching and Docking as Virtual Screening Tools", Hawkins, P.C.D., Skillman, A.G. and Nicholls, A., J. Med. Chem., 2007, 50, 74.

"Scaffold hopping, synthesis and structure-activity relationships of 5,6-diaryl-pyrazine-2-amide derivatives: A novel series of CB1 receptor antagonists". Bostrom, J., Berggren, K., Elebring, T., Greasley, Wilstermann, M., Bio. Med. Chem. (2007) 15: 4007-4084.

"Molecular Modeling Approaches for the Prediction of the Nonspecific Binding of Drugs to Hepatic Microsomes", Sykes,, M. J., Sorich, M. J., Miners, J. O., JCIM (2006) 46: 2661-2673.

"Virtual and biomolecular screening converge on a selective agonist for GPR30", Bologa, C. G., Revankar C. M., Young S. M., Edwards, B. S., Arterburn J. B., Kiselyov A. S., Parker M. A., Tkachenko S. E., Savchuck N. P., Sklar L. A., Oprea, T. I. & Prossnitz E. R.. Nature Chemical Biology (2006) 4: 175-6.

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