ROCS

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 is a powerful virtual screening tool which can rapidly identify potentially active compounds with a similar shape to a known lead compound [2]. The high speed of ROCS enables the screening of entire multi-conformer corporate collections in a single day on a single processor. Recent work indicates that ROCS is competitve with, and often superior to, structure-based approaches in virtual screening [3,4], both in terms of overall performance and consistency [5].

ROCS alignments have a number of applications: 3D QSAR, SAR analysis, understanding of scaffold diversity and detection of common binding elements[6]. ROCS alignments to crystallographic conformations have also been useful in pose prediction in the absence of a protein structure [7].

vROCS is the innovative graphical user interface that enables users to jump right into working with ROCS. vROCS also provides a powerful query editor enabling the advanced user to design complex queries. Recognizing the importance of query validation, vROCS includes a collection of statistical tools to evaluate the performance of different queries.

vROCS running ROCS in 3D mode

A database molecule overlaid on a shape query.

Features

• Returns overlays based on matching both 3D shape and chemistry
• Processes 20 to 40 compounds a second on a single CPU
• 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 Tanimoto and Tversky measure between shapes
• Intuitive graphical user interface with a query editor and statistical tools for query validation
• Multiprocessor support via OpenMPI. Can be run across multiple machines with minimal configuration and no additional installation other than ROCS
• 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] Venhorst, J., Nunez, S., Terpstra, J.W., Kruse, C.G., J. Med. Chem., 2008, 51, 3222.
[5] Sheridan, R.P., McGaughey, G.B., Cornell, W.D., J. Comput. Aided Mol. Des., 2008, 22, 257.
[6] Tuccinardi, T., Ortore, G., Amelia Santos, M., Marques, S. M., Nuti, E., Rosello, A., Martinelli, A. J. Chem., Inf. Model, 2007, 47, 2293.
[7] Sutherland, J.J., Nandigam, R.K., Erickson, J.A., Vieth, M. J. Chem., Inf. Model, 2007, 49, 1715.