Computational techniques in fragment based drug discovery

Current Topics in Medicinal Chemistry

Volumn 7, Issue 15, 2007, Pages 1509-1513

  Villar, Hugo O ^a   Hansen, Mark R ^a  

^a Altoris Inc   (United States)

Author keywords

Bioisosterism; Fragment based approaches; In silico methods; NMR guided techniques; Toxicological property

Indexed keywords

BLOOD CLOTTING FACTOR 10A INHIBITOR; LIGAND; OXIDOREDUCTASE; PROTEIN KINASE INHIBITOR; PROTEINASE INHIBITOR;

ANALYTIC METHOD; ASTHMA; BINDING AFFINITY; BINDING SITE; BIOINFORMATICS; BIOPHYSICS; CHEMICAL STRUCTURE; DATA BASE; DRUG ANALYSIS; DRUG SCREENING; FRAGMENT BASED DRUG DISCOVERY; MOLECULAR WEIGHT; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTEIN BINDING; PROTEIN INTERACTION; REVIEW; RISK ASSESSMENT; STRUCTURE ACTIVITY RELATION; TOXICITY TESTING; X RAY CRYSTALLOGRAPHY;

COMPUTATIONAL BIOLOGY; COMPUTERS; DRUG DESIGN; DRUG TOXICITY; HUMANS; LIGANDS;

EID: 35448947271     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802607782194725     Document Type: Review

References (61)

1. Villar, H.O.; Hansen, M.R.; Kho, R. Substructural Analysis in Drug Discovery. Curr. Comput. Aided Drug Des. 2007, 3, 59-67.
2. Clark, M. Generalized fragment-substructure based property prediction method. J. Chem. Inf. Model. 2005, 45, 30-8.
3. Dearden, J.C. In silico prediction of drug toxicity. J. Comput. Aided Mol. Des. 2003, 17, 119-27.
4. Erlanson, D.A. Fragment-based lead discovery: A chemical update. Curr. Opin. Biotechnol. 2006, 17, 643-52.
5. Carr, R.A.; Congreve, M.; Murray, C.W.; Rees, D.C. Fragment-based lead discovery: Leads by design. Drug Discov. Today 2005, 10, 987-92.
6. Keseru, G.M.; Makara, G.M. Hit discovery and hit-to-lead approaches. Drug Discov. Today 2006, 11, 741-748.
7. Leach, A.R.; Hann, M.M.; Burrows, J.N.; Griffen, E.J. Fragment screening: An introduction. Mol. Biosyst. 2006, 2, 430-446.
8. Mattos, C.; Ringe, D. Locating and characterizing binding sites on proteins. Nat. Biotechnol. 1996, 14, 595-599
9. Ringe, D.; What makes a binding site a binding site? Curr. Opin. Struct. Biol. 1995, 5, 825-829.
10. Caflisch, A.; Miranker, A.; Karplus, M. J. Med. Chem. 1993, 36, 2142-2167.
11. Bohm, H.J. LUDI: Rule-based automatic design of new substituents for enzyme inhibitor leads. J. Comput. Aided Mol. Des. 1992, 6, 593-606.
12. Degen, J.; Rarey, M. FlexNovo: Structure-based searching in large fragment spaces. Chem. Med. Chem. 2006, 1, 854-68.
13. Shuker, S.B.; Hajduk, P.J.; Meadows, R.P.; Fesik, S.W. Discovering high-affinity ligands for proteins: SAR by NMR. Science 1996 274, 1531-1534.
14. Hajduk, P.J. SAR by NMR: Putting the pieces together. Mol. Interv. 2006, 6, 266-272.
15. Zartler, E.R.; Shapiro, M.J. Fragonomics: Fragment-based drug discovery. Curr. Opin. Chem. Biol. 2005, 9, 366-370
16. Schade, M. NMR fragment screening: Advantages and applications. IDrugs 2006, 9, 110-3.
17. Villar, H.O.; Yan, J.; Hansen, M.R. Using NMR for ligand discovery and optimization. Curr. Opin. Chem. Biol. 2004, 8, 387-391.
18. Mattos, C.; Ringe, D. Curr. Opin. Struct. Biol. 2001, 11 761-764.
19. Blundell, T.L.; Patel, S. High-throughput X-ray crystallography for drug discovery. Curr. Opin. Pharmacol. 2004, 4, 490-496.
20. Mooij, W.T.; Hartshorn, M.J.; Tickle, I.J.; Sharff, A.J.; Verdonk, M.L.; Jhoti, H. Automated protein-ligand crystallography for structure-based drug design. Chem. Med. Chem. 2006, 1, 827-838.
21. Eisen, M.B.; Wiley, D.C.; Karplus, M.; Hubbard, R.E. HOOK: A program for finding novel molecular architectures that satisfy the chemical and steric requirements of a macromolecule binding site. Proteins 1994, 9, 199-221.
22. Schuffenhauer, A.; Ruedisser, S.; Marzinzik, A.L.; Jahnke, W.; Blommers, M.; Selzer, P.; Jacoby, E. Library design for fragment based screening. Curr. Top Med. Chem. 2005, 5(8), 751-62.
23. Lepre, C.A.; Peng, J.; Fejzo, J.; Abdul-Manan, N.; Pocas, J.; Jacobs, M.; Xie, X.; Moore, J.M. Applications of SHAPES screening in drug discovery. Comb. Chem. High Throughput Screen. 2002, 5 583-590.
24. Fielding, L.; Fletcher, D.; Rutherford, S.; Kaur, J.; Mestres, J. Exploring the active site of human factor Xa protein by NMR screening of small molecule probes. Org. Biomol. Chem. 2003, 1, 4235-4241
25. Baurin, N.; Aboul-Ela, F.; Barril, X.; Davis, B.; Drysdale, M.; Dymock, B., Finch, H.; Fromont, C.; Richardson, C.; Simmonite, H.; Hubbard, R.E. Design and characterization of libraries of molecular fragments for use in NMR screening against protein targets. J. Chem. Inf. Comput. Sci. 2004, 44, 2157-2166.
26. Mercier, K.A.; Germer, K.; Powers, R. Design and characterization of a functional library for NMR screening against novel protein targets. Comb. Chem. High Throughput Screen. 2006, 9, 515-534
27. Congreve, M.; Carr, R.; Murray, C.; Jhoti, H. Today Fragment-based lead discovery: Leads by design. Drug Discov. 2003, 8, 876-877.
28. Hajduk, P.J. Fragment-based drug design: How big is too big? J. Med. Chem. 2006, 49, 6972-6976.
29. Babaoglu, K.; Shoichet, B.K. Deconstructing fragment-based inhibitor discovery. Nat. Chem. Biol. 2006, 2, 720-723.
30. Hann, M.M.; Leach, A.R.; Harper, G. Molecular complexity and its impact on the probability of finding leads for drug discovery. J. Chem. Inf. Comput. Sci. 2001, 41, 856-864.
31. Vajda, S.; Guarnieri, F. Characterization of protein-ligand interaction sites using experimental and computational methods. Curr. Opin. Drug Discov. Devel. 2006, 9, 354-62.
32. Clark, M.; Guarnieri, F.; Shkurko, I.; Wiseman, J. Grand canonical Monte Carlo simulation of ligand-protein binding. J. Chem. Inf. Model. 2006, 46, 231-42.
33. DeLano, W.L. Unraveling hot spots in binding interfaces: Progress and challenges. Curr. Opin. Struct. Biol. 2002, 12, 14-20.
34. Arkin, M.R.; Wells, J.A. Small-molecule inhibitors of protein-protein interactions: Progressing towards the dream. Nat. Rev. Drug Discov. 2004, 3, 301-317.
35. Ciulli, A.; Williams, G.; Smith, A.G.; Blundell, T.L.; Abell, C. Probing hot spots at protein-ligand binding sites: A fragment-based approach using biophysical methods. J. Med. Chem. 2006, 49, 4992-5000.
36. Sem, D.S.; Bertolaet, B.; Baker, B.; Chang, E.; Costache, A.D.; Coutts, S.; Dong, Q.; Hansen, M.; Hong, V.; Huang, X.; Jack, R.M.; Kho, R.; Lang, H.; Ma, C.T.; Meininger, D.; Pellecchia, M.; Pierre, F.; Villar, H.; Yu, L. Systems-based design of bi-ligand inhibitors of oxidoreductases: Filling the chemical proteomic toolbox. Chem. Biol. 2004, 11, 185-94.
37. Pierce, A.C.; Rao, G.; Bemis, G.W. BREED: Generating novel inhibitors through hybridization of known ligands. Application to CDK2, p38, and HIV protease. J. Med. Chem. 2004, 47, 2768-2775.
38. Aronov, A.M.; Bemis, G.W. A minimalist approach to fragment-based ligand design using common rings and linkers: Application to kinase inhibitors. Proteins 2004, 57, 36-50.
39. Erlanson, D.A.; Hansen, S.K. Making drugs on proteins: Site-directed ligand discovery for fragment-based lead assembly. Curr. Opin. Chem. Biol. 2004, 8, 399-406.
40. Erlanson, D.A.; McDowell, R.S.; O'Brien, T. Fragment-based drug discovery. J. Med. Chem. 2004, 47, 3463-3482.
41. Fechner, U.; Schneider, G. Flux (1): A virtual synthesis scheme for fragment-based de novo design. J. Chem. Inf. Model 2006 46, 699-707.
42. Klopman, G.; Zhu, H.; Füller, M.A.; Saiakhov, R.D. Searching for an enhanced predictive tool for mutagenicity. SAR QSAR Environ. Res. 2004, 15, 251-263.
43. Rothfuss, A.; Steger-Hartmann, T.; Heinrich, N.; Wichard, J. Computational prediction of the chromosome-damaging potential of chemicals. Chem. Res. Toxicol. 2006, 19, 1313-1319
44. Kazius, J.; McGuire, R.; Bursi, R. Derivation and validation of toxicophores for mutagenicity prediction. J. Med. Chem. 2005 48, 312-320.
45. Bhavani, S.; Nagargadde, A.; Thawani, A.; Sridhar, V.; Chandra, N. Substructure-based support vector machine classifiers for prediction of adverse effects in diverse classes of drugs. J. Chem. Inf. Model. 2006, 46, 2478-86.
46. Kho, R.; Hodges, J.A.; Hansen, M.R.; Villor, H.O. Ring systems in mutagenic database. J. Med. Chem. 2005, 48, 6671-6678.
47. Johnson, D.E.; Rodgers, A.D. Computational toxicology: Heading toward more relevance in drug discovery and development. Curr. Opin. Drug Discov. Devel. 2006, 9, 29-37.
48. von Korff, M.; Sander, T. Toxicity-indicating structural patterns. J. Chem. Inf. Model. 2006, 46, 536-544.
49. Engkvist, O.; Wrede, P.; Rester, U. Prediction of CNS activity of compound libraries using substructure analysis. J. Chem. Inf. Comput. Sci. 2003, 43, 155-160.
50. Rodgers, S.; Busch, J.; Peters, H.; Christ-Hazelhof, E. Building a tree of knowledge: Analysis of bitter molecules. Chem. Senses. 2005 30, 547-57.
51. Clark, D.E.; Grootenhuis, P.D. Predicting passive transport in silico-history, hype, hope. Curr. Opin. Drug Discov. Dev. 2002 5, 382-390.
52. Jarvis, J.; Seed, M.J.; Elton, R.; Sawyer, L.; Agius, R. Prediction of asthma hazard of glutaraldehyde substitutes. Occup. Environ. Med. 2005, 62, 243-250.
53. Kazius, J.; Nijssen, S.; Kok, J.; Back, T.; Ijzerman, A.P. Substructure mining using elaborate chemical representation. J. Chem. Inf. Model. 2006, 46, 597-605.
54. Hansen, M.R.; Hodges, J.A. Identification of Unique and Redundant Scaffolds in Chemical databases. The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006. CINF 54; http://www.chemapps.com/resources.html
55. Krier, M.; Bret, G.; Rognan, D. Assessing the scaffold diversity of screening libraries. J. Chem. Inf. Model. 2006, 46, 512-524.
56. Lameijer, E.W.; Kok, J.N.; Back, T.; Ijzerman, A.P. Mining a chemical database for fragment co-ocurrence: Discovery of "chemical cliches". J. Chem. Inf. Model. 2006, 46, 553-562.
57. Warner, S.L.; Bashyam, S.; Vankayalapati, H.; Bearss, D.J.; Han, H.; Von Hoff, D.D.; Hurley, L.H. Identification of a lead small-molecule inhibitor of the Aurora kinases using a structure-assisted, fragment-based approach. Mol. Cancer Ther. 2006, 5(7), 1764-73
58. Rummey, C.; Nordhoff, S.; Thiemann, M.; Metz, G. In silico fragment-based discovery of DPP-IV S1 pocket binders. Bioorg. Med. Chem. Lett. 2006, 16(5), 1405-9.
59. Johnson, S.L.; Pellecchia, M. Structure- and fragment-based approaches to proteasse inhibition. Curr. Top Med. Chem. 2006, 6, 317-29.
60. Merckle, L.; de Andres-Gomez, A.; Dick, B.; Cox, R.J.; Godfrey, C.R. A fragment-based approach to understanding inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase. Chembiochem 2005, 6, 1866-1874.
61. Erlanson, D.A. Fragment-based lead discovery: A chemical update. Curr. Opin. Biotechnol. 2006, 17, 643-652.