Flexophore, a new versatile 3D pharmacophore descriptor that considers molecular flexibility

Journal of Chemical Information and Modeling

Volumn 48, Issue 4, 2008, Pages 797-810

  Von Korff, Modest ^a   Freyss, Joel ^a   Sander, Thomas ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CRYSTALLOGRAPHY; DATABASE SYSTEMS; GRAPH THEORY; MOLECULAR STRUCTURE;

FLEXOPHORE; MOLECULAR FLEXIBILITY; PHARMACOPHORE DESCRIPTOR;

DRUG PRODUCTS;

DRUG;

ARTICLE; CHEMISTRY; CONFORMATION;

MOLECULAR CONFORMATION; PHARMACEUTICAL PREPARATIONS;

EID: 44449143540     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci700359j     Document Type: Article

References (63)

1. Willett, P.; Barnard, J. M.; Downs, G. M. Chemical similarity searching. J. Chem. Inf. Comput. Sci. 1998, 38, 983-996.
2. Martin, Y. C. Diverse Viewpoints on Computational Aspects of Molecular Diversity. J. Comb. Chem. 2001, 3, 231-250.
3. Sheridan, R.; Kearsley, S. Why do we need so many chemical similarity search methods. Drug Discovery Today 2002, 7, 903-911.
4. Bender, A.; Glen, R. C. Molecular similarity: a key technique in molecular informatics. Org. Biomol. Chem. 2004, 2, 3204-3218.
5. Todeschini, R.; Consonni, V. Handbook of Molecular Descriptors; Wiley-VCH: Weinheim, Germany, 2000.
6. Johnson, M. A.; Maggiora, G. M. Concepts and Applications of Molecular Similarity; John Wiley & Sons: New York, 1990.
7. Patterson, D. E.; Cramer, R. D.; Ferguson, A. M.; Clark, R. D.; Weinberger, L. E. Neighborhood Behavior: A Useful Concept for Validation of "Molecular Diversity" Descriptors. J. Med. Chem. 1996, 39, 3049-3059.
8. Martin, Y. C.; Kofron, J. L.; Traphagen, L. M. Do structurally similar molecules have similar biological activity. J. Med. Chem. 2002, 45, 4350-4358.
9. Schneider, G.; Neidhart, W.; Giller, T.; Schmid, G. " Scaffoldhopping" by topological pharmacophore search: A contribution to virtual screening. Angew. Chem., Int. Ed. 1999, 38, 2894-2896.
10. Strader, C. The view from inside the receptor. J. Med. Chem. 1996, 39, 1.
11. Gund, P. Three-dimensional pharmacophoric pattern searching. Prog. Mol. Subcell. Biol. 1977, 5, 117-143.
12. McGregor, M. J.; Muskal, S. M. Pharmacophore Fingerprinting. 1. Application to QSAR and Focused Library Design. J. Chem. Inf. Comput. Sci. 1999, 39, 569-574.
13. Daylight Chemical Information Systems. Smiles ARbitrary Target Specification (SMARTS), http://www.daylight.com/dayhtml/doc/theory/theory. smarts.html (accessed Jan 18, 2008).
14. van Drie, J. H.; Weininger, D.; Martin, Y. C. ALADDIN: An integrated tool for computer-assisted molecular design and pharmacophore recognition from geometric, steric, and substructure searching of three-dimensional molecular structures. J. Comput.-Aided Mol. Des. 1989, 3, 225-251.
15. Greene, J.; Kahn, S.; Savoj, H.; Sprague, P.; Teig, S. Chemical Function Queries for 3D Database Search. J. Chem. Inf. Comput. Sci. 1994, 34, 1297-1308.
16. Pastor, M.; Cruciani, G.; McLay, I.; Pickett, S.; Clementi, S. GRid-INdependent Descriptors (GRIND): A Novel Class of Alignment-Independent Three-Dimensional Molecular Descriptors. J. Med. Chem. 2000, 43, 3233-3243.
17. Cruciani, G.; Crivori, P.; Carrupt, P. A.; Testa, B. Molecular Fields in Quantitative Structure-Permeation Relationships: the VolSurf Approach. J. Mol. Struct. 2000, 503, 17-30.
18. Goodford, P. J. A Computational Procedure for Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules. J. Med. Chem. 1985, 28, 849-857.
19. Cheeseright, T.; Mackey, M.; Rose, S.; Vinter, A. Molecular Field Extrema as Descriptors of Biological Activity: Definition and Validation. J. Chem. Inf. Model. 2006, 46, 665-676.
20. Lommerse, J. P.; Taylor, R. Characterising non-covalent interactions with the Cambridge Structural Database. J. Enzyme Inhib. 1997, 11, 223-243.
21. Bruno, I. J.; Cole, J. C.; Lommerse, J. P.; Rowland, R. S.; Taylor, R.; Verdonk, M. L. IsoStar: a library of information about nonbonded interactions. J. Comput.-Aided Mol. Des. 1997, 11, 525-537.
22. Verdonk, M. L.; Cole, J. C.; Watson, P.; Gillet, V.; Willett, P. Superstar: improved knowledge-based interaction fields for protein binding sites. J. Mol. Biol. 2001, 307, 841-859.
23. Böhm, M.; Klebe, G. Development of New Hydrogen-Bond Descriptors and Their Application to Comparative Molecular Field Analyses. J. Med. Chem. 2002, 45, 1585-1597.
24. Koshland, D. E. Enzyme flexibility and enzyme action. J. Cell. Comp. Physiol. 1959, 54, 245-258.
25. Bosshard, H. Molecular recognition by induced fit: how fit is the concept. News Physiol. Sci. 2001, 16, 171-3.
26. Martin, Y. C.; Bures, M. G.; Willett, P. Searching databases of three-dimensional structures. In Reviews in Computational Chemistry; Lipkowitz, K., Boyd, D. B., Eds.; VCH Publishers: New York, 1990; Vol. 1, pp 213-256.
27. Clark, D. E.; Willett, P.; Kenny, P. W. Pharmacophoric pattern matching in files of three-dimensional chemical structures: use of bounded distance matrices for the representation and searching of conformationally flexible molecules. J. Mol. Graphics 1992, 10, 194-204.
28. Sheridan, R. P.; Nilakantan, R.; Rusinko, A.; Bauman, I. N.; Haraki, K. S.; Venkataraghavan, R. 3DSEARCH: A System for Three-Dimensional Substructure Searching. J. Chem. Inf. Comput. Sci. 1989, 29, 255-260.
29. Martin, Y. C.; Bures, M. G.; Danaher, E. A.; DeLazzer, J.; Lico, I.; Pavlik, P. A. A fast new approach to pharmacophore mapping and its application to dopaminergic and benzodiazepine agonists. J. Comput.-Aided Mol. Des. 1993, 7, 83-102.
30. Dobler, A. V. a. M. 5D-QSAR: The Key for Simulating Induced Fit. J. Med. Chem. 2002, 45, 2139-2149.
31. Mason, J. S.; Morize, I.; Menard, P. R.; Cheney, D. L.; Hulme, C.; Labaudiniere, R. F. New 4-Point Pharmacophore Method for Molecular Similarity and Diversity Applications: Overview of the Method and Applications, Including a Novel Approach to the Design of Combinatorial Libraries Containing Privileged Substructures. J. Med. Chem. 1999, 42, 3251-3264.
32. Cruciani, G. Molecular Interaction Fields: Applications in Drug Discovery and ADME Prediction; Wiley: New York, 2006.
33. Stiefl, N.; Baumann, K. Mapping Property Distributions of Molecular Surfaces: Algorithm and Evaluation of a Novel 3D Quantitative Structure-Activity Relationship Technique. J. Med. Chem. 2003, 46, 1390-1407.
34. Bender, A.; Mussa, H. Y.; Gill, G. S.; Glen, R. C. Molecular Surface Point Environments for Virtual Screening and the Elucidation of Binding Patterns (MOLPRINT 3D). J. Med. Chem. 2004, 47, 6569-6583.
35. Senese, C. L.; Duca, J.; Pan, D.; Hopfinger, A. J.; Tseng, Y. J. 4D-Fingerprints, Universal QSAR and QSPR Descriptors. J. Chem. Inf. Comput. Sci. 2004, 44, 1526-1539.
36. Zhang, Q.; Muegge, I. Scaffold Hopping through Virtual Screening Using 2D and 3D Similarity Descriptors: Ranking, Voting, and Consensus Scoring. J. Med. Chem. 2006, 49, 1536-1548.
37. Brown, R. D.; Martin, Y. C. Use of Structure-Activity Data To Compare Structure-Based Clustering Methods and Descriptors for Use in Compound Selection. J. Chem. Inf. Comput. Sci. 1996, 36, 572-584.
38. Brown, R. D.; Martin, Y. C. The Information Content of 2D and 3D Structural Descriptors Relevant to Ligand-Receptor Binding. J. Chem. Inf. Comput. Sci. 1997, 37, 1-9.
39. Matter, H.; Pötter, T. Comparing 3D Pharmacophore Triplets and 2D Fingerprints for Selecting Diverse Compound Subsets. J. Chem. Inf. Comput. Sci. 1999, 39, 1211-1225.
40. Schuffenhauer, A.; Gillet, V. J.; Willett, P. Similarity Searching in Files of Three-Dimensional Chemical Structures: Analysis of the BIOSTER Database Using Two-Dimensional Fingerprints and Molecular Field Descriptors. J. Chem. Inf. Comput. Sci. 2000, 40, 295-307.
41. Andrews, K. M.; Cramer, R. D. Toward General Methods of Targeted Library Design: Topomer Shape Similarity Searching with Diverse Structures as Queries. J. Med. Chem. 2000, 43, 1723-1740.
42. Makara, G. M. Measuring molecular similarity and diversity: total pharmacophore diversity. J. Med. Chem. 2001, 44, 3563-71.
43. Jenkins, J. L.; Glick, M.; Davies, J. W. A 3D similarity method for scaffold hopping from known drugs or natural ligands to new chemotypes. J. Med. Chem. 2004, 47, 144-59.
44. Hert, J.; Willett, P.; Wilton, D. J.; Acklin, P.; Azzaoui, K.; Jacoby, E.; Schuffenhauer, A. Comparison of fingerprint-based methods for virtual screening using multiple bioactive reference structures. J. Chem. Inf. Comput. Sci. 2004, 44, 1177-85.
45. Allinger, N. L.; Zhou, X.; Bergsma, J. Molecular Mechanics Parameters. J. Mol. Struct 1994, 312, 69-83.
46. Berman, H. M.; 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.
47. ChemAxon, GenerateMD. http://www.chemaxon.com/jchem/doc/user/fingerprint. html (accessed Nov 8, 2007).
48. von Korff, M.; Sander, T. Toxicity-Indicating Structural Patterns. J. Chem. Inf. Model 2006, 46, 536-544.
49. Thomson Investigational Drugs Database (IDDB). http://scientific.thomson. com/products/iddb/ (accessed Sep 2004).
50. Orlek, B. S.; Blaney, F. E.; Brown, F.; Clark, M. S. G.; Hadley, M. S.; Hatcher, J.; Riley, G. J.; Rosenberg, H. E.; Wadsworth, H. J.; Wyman, P. Comparison of azabicyclic esters and oxadiazoles as ligands for the muscarinic receptor. J. Med. Chem. 1991, 34, 2726-2735.
51. Stahl, M.; Rarey, M. Detailed Analysis of Scoring Functions for Virtual Screening. J. Med. Chem. 2001, 44, 1035-1042.
52. Bender, A. Cheminformatics. http://www.cheminformatics.org/menu.shtml (accessed Nov 8, 2005).
53. Korff, M. v.; Steger, M. GPCR-Tailored Pharmacophore Pattern Recognition of Small Molecular Ligands. J. Chem. Inf. Comput. Sci. 2004, 44, 1137-1147.
54. Carhart, R. E.; Smith, D. H.; Venkataraghavan, R. Atom Pairs as Molecular Features in Structure-Activity Studies: Definition and Applications. J. Chem. Inf. Comput. Sci. 1985, 25, 64-73.
55. Baumann, K. An alignment-independent versatile structure descriptor for QSAR and QSPR based on the distribution of molecular features. J. Chem. Inf. Comput. Sci. 2002, 42, 26-35.
56. Yuan, S.; Zheng, C.; Zhao, X.; Zeng, F. Identification of maximal common substructures in structure/activity studies. Anal. Chim. Acta 1990, 235, 239-241.
57. McGregor, J. J. Backtrack search algorithms and the maximal common subgraph problem. Software - Pract. Exper. 1982, 12, 23-34.
58. Raymond, J. W.; Willett, P. Maximum common subgraph isomorphism algorithms for the matching of chemical structures. J. Comput-Aided Mol. Des. 2002, 16, 521-33.
59. Xu, H.; Izrailev, S.; Agrafiotis, D. K. Conformational sampling by self-organization. J. Chem. Inf. Comput. Sci. 2003, 43, 1186-1191.
60. Gohlke, H.; Hendlich, M.; Klebe, G. Knowledge-based scoring function to predict protein-ligand interactions. J. Mol. Biol. 2000, 295, 337-56.
61. Sheridan, R. P.; Miller, M. D.; Underwood, D. J.; Kearsley, S. K. Chemical Similarity Using Geometric Atom Pair Descriptors. J. Chem. Inf. Comput. Sci. 1996, 36, 128-136.
62. Rusinko, A. I.; Skell, J. M.; Balducci, R.; McGarity, C. M.; Pearlman, R. S. CONCORD: A Program for the Rapid Generation of High Quality Approximate 3-Dimensional Molecular Structures; The University of Texas at Austin and Tripos Associates: St. Louis, MO, 1988.
63. Agrafiotis, D. K.; Gibbs, A. C.; Zhu, F.; Izrailev, S.; Martin, E. Conformational Sampling of Bioactive Molecules: A Comparative Study. J. Chem. Inf. Model. 2007, 47, 1067-1086.