Systematic identification and classification of three-dimensional activity cliffs

Journal of Chemical Information and Modeling

Volumn 52, Issue 6, 2012, Pages 1490-1498

  Hu, Ye ^a   Furtmann, Norbert ^a   Gütschow, Michael ^a   Bajorath, Jürgen ^a  

^a UNIVERSITY OF BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING ENERGY; LIGANDS; PROTEINS; X RAYS;

ENERGY FUNCTIONS; INTERACTION PATTERN; ORDERS OF MAGNITUDE; PROTEIN DATA BANK; SHORT RANGE INTERACTIONS; STRUCTURE-BASED DESIGNS; SYSTEMATIC IDENTIFICATION; THREEDIMENSIONAL (3-D);

LANDFORMS;

LIGAND;

ARTICLE; CHEMICAL STRUCTURE; PROTEIN DATABASE; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; DATABASES, PROTEIN; LIGANDS; MODELS, MOLECULAR; MOLECULAR STRUCTURE;

EID: 84862854379     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci300158v     Document Type: Article

References (24)

1. Maggiora, G. M. On Outliers and Activity Cliffs - Why QSAR often Disappoints J. Chem. Inf. Model. 2006, 46, 1535-1535
2. Vogt, M.; Huang, Y.; Bajorath, J. From Activity Cliffs to Activity Ridges: Informative Data Structures for SAR Analysis J. Chem. Inf. Model. 2011, 51, 1848-1856
3. Stumpfe, D.; Bajorath, J. Exploring Activity Cliffs in Medicinal Chemistry J. Med. Chem. 2012, 55, 2932-2942
4. Bajorath, J.; Peltason, L.; Wawer, M.; Guha, R.; Lajiness, M. S.; Van Drie, J. H. Navigating Structure-Activity Landscapes Drug Discovery Today 2009, 14, 698-705
5. Wassermann, A. M.; Dimova, D.; Bajorath, J. Comprehensive Analysis of Single- and Multi-Target Activity Cliffs Formed by Currently Available Bioactive Compounds Chem. Biol. Drug Des. 2011, 78, 224-228
6. Wassermann, A. M.; Wawer, M.; Bajorath, J. Activity Landscape Representations for Structure-Activity Relationship Analysis J. Med. Chem. 2010, 53, 8209-8223
7. Medina-Franco, J. L.; Martínez-Mayorga, K.; Bender, A.; Marín, R. M.; Giulianotti, M. A.; Pinilla, C.; Houghten, R. A. Characterization of Activity Landscapes using 2D and 3D Similarity Methods: Consensus Activity Cliffs J. Chem. Inf. Model. 2009, 49, 477-491
8. Sisay, M. T.; Peltason, L.; Bajorath, J. Structural Interpretation of Activity Cliffs Revealed by Systematic Analysis of Structure-Activity Relationships in Analog Series J. Chem. Inf. Model. 2009, 49, 2179-2189
9. Seebeck, B.; Wagener, M.; Rarey, M. From Activity Cliffs to Target-specific Scoring Models and Pharmacophore Hypotheses ChemMedChem 2011, 6, 1630-1639
10. Hu, Y.; Bajorath, J. Exploration of 3D Activity Cliffs on the Basis of Compound Binding Modes and Comparison of 2D and 3D-cliffs J. Chem. Inf. Model. 2012, 52, 670-677
11. Peltason, L.; Bajorath, J. Molecular Similarity Analysis Uncovers the Presence of Heterogeneous Structure-Activity Relationships and Variable Activity Landscapes within Active Sites Chem. Biol. 2007, 14, 489-497
12. Berman, H.; Henrick, K.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank Nucleic Acids Res. 2000, 28, 235-242
13. Berman, H.; Henrick, K.; Nakamura, H.; Markley, J. L. The Worldwide Protein Data Bank (wwPDB) Nucleic Acids Res. 2007, 35, D301-D303
14. RCSB Protein Data Bank. http://www.rcsb.org (accessed March 1, 2012).
15. UniProtConsortium. The Universal Protein Resource (UniProt) in 2010. Nucleic Acids Res. 2010, 38, D142-D148.
16. Gaulton, A.; Bellis, L. J.; Bento, A. P.; Chambers, J.; Davies, M.; Hersey, A.; Light, Y.; McGlinchey, S.; Michalovich, D.; Al-Lazikani, B.; Overington, J. P. ChEMBL: A Large-scale Bioactivity Database for Drug Discovery Nucleic Acids Res. 2012, 40, D1100-D1107
17. ChEMBL. http://www.ebi.ac.uk/chembldb/ (accessed March 1, 2012).
18. Liu, T.; Lin, Y.; Wen, X.; Jorissen, R. N.; Gilson, M. K. BindingDB: a Web-Accessible Database of Experimentally Determined Protein-Ligand Binding Affinities Nucleic Acids Res. 2007, 35, D198-D201
19. BindingDB. http://www.bindingdb.org/ (accessed March 1, 2012).
20. Willett, P. Searching Techniques for Databases of Two- and Three-Dimensional Structures J. Med. Chem. 2005, 48, 4183-4199
21. MACCS Structural Keys; Symyx Software: San Ramon, CA, 2005.
22. MOE (Molecular Operating Environment); Chemical Computing Group Inc.: Montreal, Quebec, Canada, 2011.
23. Clark, A. M.; Labute, P. 2D Depiction of Protein-Ligand Complexes J. Chem. Inf. Model. 2007, 47, 1933-1944
24. Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N. S.; Wang, J. T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: a Software Environment for Integrated Models of Biomolecular Interaction Networks Genome Res. 2003, 13, 2498-2504