Designed for use with the large libraries required for computer-aided drug design, OMEGA generates multi-conformer structure databases with unprecedented speed and reliability. Conformational expansion of drug-like molecules can be performed in fractions of a second, yielding a throughput of hundreds of thousands of compounds per processor per day. Scientists at AstraZeneca found OMEGA to be more reliable in reproducing crystal structures than programs taking orders of magnitude more time [1]. Researchers at Vertex concluded, "Omega achieves the best balance between speed and performance among the programs examined, and it appears to be the most suitable tool for conformational analysis on large chemical databases." [2]

The Xray crystal structure of Lipitor in its active conformation (green) overlaid by an Omega conformation which reproduces the active conformation to within 0.75 Angstrom rms. Select image to enlarge.

The primary features of OMEGA include:

• Very rapid, systematic conformer search
• Converts from 1D or 2D to 3D using distance bounds methods
• Optionally refines input or output structures with MMFF and solvation effects [3]
• Diverse ensemble selection based on RMS distance
• User-configurable search resolution
• Automatic superposition of structural features
• OEChemplete – all I/O and molecular information processing by OEChem
• Robust reading and specification-compliant writing of SMILES, SLN, SDF, MOL, MOL2, PDB, FASTA, MOPAC, MacroModel, XYZ, and OEBinary formats
• Support for LINUX, HP-UX, Tru64, AIX, IRIX, Solaris, Windows, and OS X
• 64-bit processing on HP-UX, Tru64, AIX, IRIX, Itanium®2 and PowerPC Linux
• Distributed processing via PVM for most Unix platforms
• Useful for generating input structures for other software, e.g. FRED or ROCS

[1] Reproducing the conformations of protein-bound ligands: A critical evaluation of several popular conformational searching tools: Boström, J., J. Comp.-Aid. Mol. Design, 2001, 15, 1137; Assessing the performance of OMEGA with respect to retrieving bioactive conformations: Boström, J., Greenwood J.R., and Gottfries, J., J. Mol. Graph. Mod., 2003, 21, 449-462.

[2] Conformational Analysis of Drug-Like Molecules Bound to Proteins: An Extensive Study of Ligand Reorganization upon Binding: Perola, E. and Charifson, P.S., J. Med. Chem., 2004, 47, 2499-2510.

[3] Merck Molecular Force Field: I-V: Halgren, T.A., J. Comp. Chem, 1996, 17, 490-641; VI-VII: Ibid. 1999, 20, 720-748; The Sheffield Solvation Model: Sykes, M., Pickup, B. and Grant, A., In preparation.

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