Daylight Theory Manual Daylight Theory Manual Table of Contents Daylight Theory Manual....................................................................................................................................1 1. Introduction..........................................................................................................................................1 2. Molecules and Reactions in A Computer............................................................................................1 2.1 Representing Molecules..............................................................................................................1 2.2 Analyzing Molecules...................................................................................................................2 2.2.1 Cycles.................................................................................................................................2 2.2.2 Bond Type, Bond Order, and Aromaticity........................................................................2 2.2.3 Symmetry...........................................................................................................................3 2.2.4 Canonical Labeling............................................................................................................3 2.2.5 Chirality.............................................................................................................................3 2.3 Representing Reactions...............................................................................................................3 2.4 Depictions....................................................................................................................................4 3. SMILES - A Simplified Chemical Language......................................................................................5 3.1 Canonicalization..........................................................................................................................6 3.2 SMILES Specification Rules.......................................................................................................6 3.2.1 Atoms.................................................................................................................................6 3.2.2 Bonds.................................................................................................................................7 3.2.3 Branches.............................................................................................................................8 3.2.4 Cyclic Structures................................................................................................................8 3.2.5 Disconnected Structures....................................................................................................9 3.3 Isomeric SMILES........................................................................................................................9 3.3.1 Isotopic Specification......................................................................................................10 3.3.2 Configuration Around Double Bonds..............................................................................10 3.3.3. Configuration Around Tetrahedral Centers....................................................................10 3.3.4 General Chiral Specification............................................................................................12 3.4 SMILES Conventions................................................................................................................13 3.4.1 Hydrogens........................................................................................................................13 3.4.2 Aromaticity......................................................................................................................14 3.4.3 Aromatic Nitrogen Compounds.......................................................................................15 3.4.4 Bonding Conventions......................................................................................................15 3.4.5 Tautomers........................................................................................................................15 3.5 Extensions for Reactions...........................................................................................................16 3.5.1 Reaction Atom Maps.......................................................................................................17 3.5.2 Hydrogens........................................................................................................................18 3.6 Acknowledgments.....................................................................................................................19 4. SMARTS - A Language for Describing Molecular Patterns.............................................................19 4.1 Atomic Primitives......................................................................................................................19 4.2 Bond Primitives.........................................................................................................................20 4.3 Logical Operators......................................................................................................................21 4.4 Recursive SMARTS..................................................................................................................21 4.5 Component-level grouping of SMARTS..................................................................................22 4.6 Reaction Queries.......................................................................................................................22 4.7 SMARTS Versus SMILES........................................................................................................24 4.8 Efficiency Considerations.........................................................................................................25 4.9 Examples...................................................................................................................................25 5. SMIRKS - A Reaction Transform Language.....................................................................................26 5.1 Description................................................................................................................................26 5.2 Representation...........................................................................................................................27 i Daylight Theory Manual Table of Contents Daylight Theory Manual 5.3 Transform Grammar..................................................................................................................27 5.4 Examples...................................................................................................................................28 6. Fingerprints - Screening and Similarity.............................................................................................30 6.1 A Brief History of Screening Large Databases.........................................................................31 6.1.1 Structural keys.................................................................................................................32 6.1.2 Fingerprints......................................................................................................................33 6.1.3 Variable-sized Fingerprints..............................................................................................34 6.1.4 In-memory Screening......................................................................................................35 6.2 Fingerprints and Reactions........................................................................................................36 6.2.1 Structural Reaction Fingerprints............................................................................................36 6.2.2 Reaction Difference Fingerprints...........................................................................................36 6.3 Similarity Measures...................................................................................................................37 6.3.1 Tversky Index..................................................................................................................39 6.3.2 User-defined and Named Similarity indexes...................................................................40 7. THOR - Chemical Database System..................................................................................................42 7.1 Hash Table.................................................................................................................................42 7.2 Servers and Clients....................................................................................................................44 7.3 Identifiers...................................................................................................................................45 7.4 The THOR Data Tree................................................................................................................46 7.5 Datatypes...................................................................................................................................48 7.5.1 Creating Datatypes...........................................................................................................48 7.5.2 Standardization................................................................................................................49