Shape Similarity for Virtual Screening & Lead Hopping

ROCS is a 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.

ROCS' high speed makes it possible, for virtual screening, to search multi-conformer representations of corporate collections in a day on a single processor to find active compounds with similar shape to a lead compound (lead-hopping [2]). Recent work suggests that ROCS could be more consistent than, and often superior to, docking programs as virtual screening tools [3].

ROCS alignments have a number of applications: 3D QSAR, SAR analysis, understanding of scaffold diversity and detection of common binding elements. ROCS has recently been shown to be very effective in pose prediction [4].

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

Features

• Returns overlays based on matching both 3D shape and chemistry
• Processes 8 to 10 compounds a second
• Overlays are intuitive and visually informative when viewed in standard visualizers (e.g. VIDA)
• Chemistry matching based on user-definable 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
• Reports rigorous Tanomoto and Tversky measure between shapes
• Distributed processing via PVM for most Unix platforms

For ROCS and All OpenEye Products

• Multiple file format handling: robust reading and specification-compliant writing of: SMILES, SLN, SDF, MOL, MOL2, PDB, FASTA, MOPAC, MacroModel, XYZ, CCP4, XPLOR, and OEBinary.
• Platform independence: support for Linux, Windows, Mac OS X and many flavors of Unix in both 32 and 64 bit.

[1] Grant, J.A., Gallardo, M.A., Pickup, B., J. Comp. Chem., 1996, 17, 1653.
[2] Rush, T.S., Grant, J.A., Mosyak, L., Nicholls, A., J. Med. Chem., 2005, 48, 1489.
[3] Hawkins, P.C.D., Skillman, A.G., Nicholls, A., J. Med. Chem., 2007, 50, 74.
[4] Sutherland, J.J., Nandigam, R.K., Erickson, J.A., Vieth, M. J. Chem., Inf. Model, 2007, 47, 2293.

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