Canonicalized systematic nomenclature in chemoinformatics And some new canonicalization tools from OpenEye Jeremy J. Yang 3600 Cerrillos Road Suite 1107 Santa Fe, New Mexico 87507 505.473.7385 info@eyesopen.com www.eyesopen.com Introduction Canonicalization in chemoinformatics facilitates rigorous, unambiguous expression and handling of chemical data and knowledge. However, just as chemistry encompasses multiple levels of abstraction and modelling, no single canonicalization method is sufficient to solve all problems. This study reviews some existing canonicalization methodology and describes new methods implemented by chemoinformatics library OEChem and other OpenEye tools. Aha! -- Chemo-taxonomy is a “stranded hierarchy” The Morgan algorithm was a huge step forward, but the basic algorithm has some shortcomings, in performance and comprehensiveness, which have been corrected by subsequent investigators. The resulting methods have been implemented and widely used in large scale database systems. Some key contributions: • Morgan, 1965 à note to Harry: “You da man!” à CAS • Wipke & Dyott, 1974 à stereo-enhanced Morgan à MDL • Jochum & Gasteiger, 1977 à Morgan refinement à CACTVS • Shelley & Munk, 1977 à Morgan refinement • Weininger, 1988 à CANSMI canonical line notation à Daylight • Bradshaw, 1998 à parent compounds à GSK,Daylight • Delany & Sayle, 1999 à tautomers à OpenEye • INChi, 2004 à global canonical line notation Fig 2: Morgan slow due to symmetry. 1. Morgan, H. L., "Generation of a unique machine description for chemical structures - A technique developed at Chemical Abstracts Services", J. Chem. Doc. 1965, 5, 107. 2. Stereochemically unique naming algorithm, W. Todd Wipke, Thomas M. Dyott; J. Am. Chem. Soc.; 1974; 96(15); 4834-4842. 3. Canonical Numbering and Constitutional Symmetry, Clemens Jochum and Johann Gasteiger, J. Chem. Inf. Comput. Sci.; 1977; 17(2); 113-117. 4. Computer Perception of Topological Symmetry, Craig A. Shelley, Morton E. Munk; J. Chem. Inf. Comput. Sci.; 1977; 17(2); 110-113. 5. An Approach to the Assignment of Canonical Connection Tables and Topological Symmetry Perception, Craig A. Shelley, Morton E. Munk, J. Chem. Inf. Comput. Sci.; 1979; 19(4); 247-250. 6. David Weininger, Arthur Weininger and Joseph L. Weininger, "SMILES 2: Algorithm for Generation of Unique SMILES Notation", Journal of Chemical Information and Computer Science (JCICS), Vol. 29, No. 2, pp. 97-101, 1989. 7. A beginner's guide to responsible parenting or knowing your roots, www.daylight.com/meetings/emug98/Bradshaw/, EuroMUG '98, Cambridge, UK, Oct 1998. 8. Canonicalization and Enumeration of Tautomers, Jack Delany and Roger Sayle, www.daylight.com/meetings/emug99/Delany/taut_html/sld001.htm EuroMUG '99, Cambridge, UK, Oct 1999. 9. Hooked on Protonics, Roger Sayle and Geoff Skillman, www.eyesopen.com/about/events/presentations/acs02/sld001.htm, 224th ACS National Meeting, Boston, Aug 2002. 10. Introduction to Chemical Info Systems, John Bradshaw, www.daylight.com/meetings/emug02/Bradshaw/Training/, Euromug02 24th-26th September 2002, Cambridge UK 11. That INChIFeeling, www.reactivereports.com/40/40_3.html, Reactive Reports, Sep 2004 (issue 40) 12. OEChem, OpenEye Scientific Software, 2002. 13. QuacPac, OpenEye Scientific Software, 2004. References • subatomic à atoms à molecules • normal weight atoms à isotopes • Kekule molecule model à aromatic molecule models • non-stereo molecule à stereoisomers • single molecule à combinatorial libraries • single molecule à queries • small molecule à macromolecule + cofactors + ligands • single molecule à Markush structures • single molecule à tautomer set • single molecule à pKa states • single molecule à reactions • 2D à 3D There is a hierarchical relationship among some of these expansions while some are independent. For example, combinatorial library may involve stereoisomeric individuals or non-stereo. For every combination of molecular representations, ca