Detection and assignment of common scaffolds in project databases of lead molecules

Journal of Medicinal Chemistry

Volumn 52, Issue 2, 2009, Pages 469-483

  Clark, Alex M ^a   Labute, Paul ^a  

^a INSTITUTE FOR RESEARCH IN IMMUNOLOGY AND CANCER   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG;

ALGORITHM; ARTICLE; DATA BASE; DRUG DETERMINATION; DRUG STRUCTURE; MOLECULE; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ALGORITHMS; DATABASE MANAGEMENT SYSTEMS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 60549099994     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm801098a     Document Type: Article

References (23)

1. Agrafiotis, D. K.; Shemanarev, M.; Connolly, P. J.; Farnum, M.; Lobanov, V. S. SAR Maps: A New SAR Visualization Technique for Medicinal Chemists. J. Med. Chem. 2007, 50, 5926-5937.
2. Kubinyi, H. Free Wilson Analysis. Theory, Applications and its Relationship to Hansch Analysis. Quantum Struct. -Act. Relat. 1988. 7, 121-133.
3. Guan, H.; Laird, A. D.; Blake, R. A.; Tang, C.; Liang, C. Design and synthesis of aminopropyl tetrahydroindole-based indolin-2-ones as selective and potent inhibitors of Src and Yes tyrosine kinase. Bioorg. Med. Chem. Lett. 2004, 14, 187-190.
4. (a) Bemis, G. W.; Murcko, M. A. The Properties of Known Drugs. 1. Molecular Frameworks. J. Med. Chem. 1996, 39, 2887-2893.
5. (b) Xu, J. A New Approach to Finding Natural Chemical Classes. J. Med. Chem. 2002, 45, 5311-5320.
6. Wilkens, S. J.; Janes, J.; Su, A. I. HierS: Hierarchical Scaffold Clustering Using Topological Chemical Graphs. J. Med. Chem. 2005, 48, 3182-3195.
7. Krier, M.; Bret, G.; Rognan, D. Assessing the Scaffold Diversity of Screening Libraries. J. Chem. Inf. Model. 2006, 46, 512-524.
8. (e) Ertl, P.; Jelfs, S.; Mühlbacher, J.; Schuffenhauer, A.; Selzer, P. Quest for the Rings. In Silico Exploration of Ring Universe To Identify Novel Bioactive Heteroaromatic Scaffolds. J. Med. Chem. 2006, 49, 4568-4573.
9. (f) Shelat, A. A.; Guy, R. K. Scaffold composition and biological relevance of screening libraries. Nat. Chem. Biol. 2007, 3, 442-446.
10. (a) Raymond, J.; Gardiner, E.; Willett, P. RASCAL: Calculation of Graph Similarity using Maximum Common Edge Subgraphs. Comput. J. 2002, 45, 631-644.
11. (b) Garc, G. C.; Ruiz, I. L.; Gomez- Nieto, M.A. Step-by-Step Calculation of All Maximum Common Substructures through a Constraint Satisfaction Based Algorithm. J. Chem. Inf. Comput. Sci. 2004, 44, 30-41.
12. Gardiner, E. J.; Gillet, V. J.; Willett, P.; Cosgrove, D. A. Representing Clusters Using a Maximum Common Edge Substructure Algorithm Applied to Reduced Graphs and Molecular Graphs. J. Chem. Inf. Model. 2007, 47, 354-366.
13. Barker, E. J.; Buttar, D.; Cosgrove, D. A.; Gardiner, E. J.; Kitts, P.; Willett, P.; Gillet, V. J. Scaffold Hopping Using Clique Detection Applied to Reduced Graphs. J. Chem. Inf. Model. 2006, 46, 503-511.
14. Schuffenhauer, A.; Ertl, P.; Roggo, S.; Wetzel, S.; Koch, M. A.; Waldmann, H. The Scaffold Tree-Visualization of the Scaffold Universe by Hierarchical Scaffold Classification. J. Chem. Inf. Model. 2007, 47, 47-58.
15. Weininger, D. SMILES 1. Introduction and Encoding Rules. J. Chem. Inf. Comput. Sci. 1988, 28, 31-36.
16. McGregor, M. J.; Pallai, P. V. Clustering of Large Databases of Compounds: Using the MDL "Keys" as Structural Descriptors. J. Chem. Inf. Comput. Sci. 1997, 37, 443-448.
17. In this work, values of S are between 0 and 1, these values representing the extremes of no common features in their substitution patterns to identical substitution patterns. Intermediate values can be obtained by similarity between the R-groups at each position, e.g., by the average of the Tanimoto coefficients, using structural fingerprints such as MACCS.
18. Labute, P. Protonate3D: Assignment of Ionization States and Hydrogen Coordinates to Macromolecular Structures. Proteins: Struct., Funct., Bioinf. 2008, in press.
19. (a) Desmet, J.; de Maeyer, M.; Hazes, B.; Lasters, I. The dead-end elimination theorem and its use in protein side-chain positioning. Nature 1992, 356, 539-542.
20. (b) Pierce, N. A.; Spriet, J. A.; Desmet, J.; Mayo, S. L. Conformational splitting: A more powerful criterion for dead-end elimination. Science 2008, 21, 999-1009.
21. (a) Clark, A. M.; Labute, P. 2D Depiction of Protein-Ligand Complexes. J. Chem. Inf. Model. 2007, 47, 1933-1944.
22. (b) Clark, A. M.; Labute, P.; Santavy, M. 2D Structure Depiction. J. Chem. Inf. Model 2006, 46, 1107-1123.
23. The source code for the algorithms described within, and those referred to, is packaged as part of MOE and may be examined and used under the terms of the MOE user license, which is available from the Chemical Computing Group, Inc., 1010 Sherbrooke Street West, Suite 910, Montréal, Québec, Canada; http://www.chemcomp.com (accessed Aug 18, 2008).