Approximating protein flexibility through dynamic pharmacophore models: Application to fatty acid amide hydrolase (FAAH)

Journal of Chemical Information and Modeling

Volumn 51, Issue 12, 2011, Pages 3247-3253

  Bowman, Anna L ^a   Makriyannis, Alexandros ^a  

^a NORTHEASTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDES; HYDROLASES; IMPORTANCE SAMPLING; MOLECULAR DYNAMICS; PHARMACODYNAMICS; X RAYS;

CONFORMATIONAL ENSEMBLE; CONFORMATIONAL SAMPLINGS; DRUG DISCOVERY METHODS; FATTY ACID AMIDE HYDROLASE; MOLECULAR DYNAMICS SIMULATIONS; PHARMACOPHORE MODELS; PROTEIN CONFORMATION; STRUCTURE BASED DRUG DESIGNS;

FATTY ACIDS;

AMIDASE; ENZYME INHIBITOR; FATTY ACID AMIDASE; FATTY-ACID AMIDE HYDROLASE;

ANIMAL; ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; DRUG DESIGN; HUMAN; METABOLISM; PROTEIN CONFORMATION; RAT; X RAY CRYSTALLOGRAPHY;

AMIDOHYDROLASES; ANIMALS; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; ENZYME INHIBITORS; HUMANS; MODELS, MOLECULAR; PROTEIN CONFORMATION; RATS;

EID: 84555220607     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci200371z     Document Type: Article

References (54)

1. Cozzini, P.; Kellogg, G. E.; Spyrakis, F.; Abraham, D. J.; Costantino, G.; Emerson, A.; Fanelli, F.; Gohlke, H.; Kuhn, L. A.; Morris, G. M.; Orozco, M.; Pertinhez, T. A.; Rizzi, M.; Sotriffer, C. A. Target Flexibility: An Emerging Consideration in Drug Discovery and Design J. Med. Chem. 2008, 51, 6237-6255
2. Teague, S. J. Implications of protein flexibility for drug discovery Nat. Rev. Drug Discovery 2003, 2, 527-541
3. Erickson, J. A.; Jalaie, M.; Robertson, D. H.; Lewis, R. A.; Vieth, M. Lessons in molecular recognition: The effects of ligand and protein flexibility on molecular docking accuracy J. Med. Chem. 2004, 47, 45-55
4. Carlson, H. A. Protein flexibility and drug design: how to hit a moving target Curr. Opin. Chem. Biol. 2002, 6, 447-452
5. Sherman, W.; Day, T.; Jacobson, M. P.; Friesner, R. A.; Farid, R. Novel procedure for modeling ligand/receptor induced fit effects J. Med. Chem. 2006, 49, 534-553
6. Amaro, R. E.; Baron, R.; McCammon, J. A. An improved relaxed complex scheme for receptor flexibility in computer-aided drug design J. Comput. Aided Mol. Des. 2008, 22, 693-705
7. Cravatt, B. F.; Giang, D. K.; Mayfield, S. P.; Boger, D. L.; Lerner, R. A.; Gilula, N. B. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides Nature 1996, 384, 83-87
8. Godlewski, G.; Alapafuja, S. O.; Batkai, S.; Nikas, S. P.; Cinar, R.; Offertaler, L.; Osei-Hyiaman, D.; Liu, J.; Mukhopadhyay, B.; Harvey-White, J.; Tam, J.; Pacak, K.; Blankman, J. L.; Cravatt, B. F.; Makriyannis, A.; Kunos, G. Inhibitor of Fatty Acid Amide Hydrolase Normalizes Cardiovascular Function in Hypertension without Adverse Metabolic Effects. Chem. Biol. 2010, 17, 1256-1266.
9. Hwang, J.; Adamson, C.; Butler, D.; Janero, D. R.; Makriyannis, A.; Bahr, B. A. Enhancement of endocannabinoid signaling by fatty acid amide hydrolase inhibition: A neuroprotective therapeutic modality. Life Sci. 2010, 86, 615-623.
10. Cravatt, B. F.; Demarest, K.; Patricelli, M. P.; Bracey, M. H.; Giang, D. K.; Martin, B. R.; Lichtman, A. H. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 9371-9376
11. Ahn, K.; Johnson, D. S.; Mileni, M.; Beidler, D.; Long, J. Z.; McKinney, M. K.; Weerapana, E.; Sadagopan, N.; Liimatta, M.; Smith, S. E.; Lazerwith, S.; Stiff, C.; Kamtekar, S.; Bhattacharya, K.; Zhang, Y. H.; Swaney, S.; Van Becelaere, K.; Stevens, R. C.; Cravatt, B. F. Discovery and Characterization of a Highly Selective FAAH Inhibitor that Reduces Inflammatory Pain Chem. Biol. 2009, 16, 411-420
12. Gobbi, G.; Bambico, F. R.; Mangieri, R.; Bortolato, M.; Campolongo, P.; Solinas, M.; Cassano, T.; Morgese, M. G.; Debonnel, G.; Duranti, A.; Tontini, A.; Tarzia, G.; Mor, M.; Trezza, V.; Goldberg, S. R.; Cuomo, V.; Piomelli, D. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 18620-18625
13. Cravatt, B. F.; Saghatelian, A.; Hawkins, E. G.; Clement, A. B.; Bracey, M. H.; Lichtman, A. H. Functional disassociation of the central and peripheral fatty acid amide signaling systems Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 10821-10826
14. Jayamanne, A.; Greenwood, R.; Mitchell, V. A.; Aslan, S.; Piomelli, D.; Vaughan, C. W. Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models Br. J. Pharmacol. 2006, 147, 281-288
15. Romero, F. A.; Du, W.; Hwang, I.; Rayl, T. J.; Kimball, F. S.; Leung, D.; Hoover, H. S.; Apodaca, R. L.; Breitenbucher, J. G.; Cravatt, B. F.; Boger, D. L. Potent and selective alpha-ketoheterocycle-based inhibitors of the anandamide and oleamide catabolizing enzyme, fatty acid amide hydrolase J. Med. Chem. 2007, 50, 1058-1068
16. Ahn, K.; Johnson, D. S.; Fitzgerald, L. R.; Liimatta, M.; Arendse, A.; Stevenson, T.; Lund, E. T.; Nugent, R. A.; Nomanbhoy, T. K.; Alexander, J. P.; Cravatt, B. F. Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity Biochemistry 2007, 46, 13019-13030
17. Deng, H. F. Recent advances in the discovery and evaluation of fatty acid amide hydrolase inhibitors Expert Opin. Drug Discovery 2010, 5, 961-993
18. Minkkila, A.; Saario, S. M.; Nevalainen, T. Discovery and Development of Endocannabinoid-Hydrolyzing Enzyme Inhibitors Curr. Top. Med. Chem. 2010, 10, 828-858
19. Bracey, M. H.; Hanson, M. A.; Masuda, K. R.; Stevens, R. C.; Cravatt, B. F. Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling Science 2002, 298, 1793-1796
20. Mileni, M.; Johnson, D. S.; Wang, Z. G.; Everdeen, D. S.; Liimatta, M.; Pabst, B.; Bhattacharya, K.; Nugent, R. A.; Kamtekar, S.; Cravatt, B. F.; Ahn, K.; Stevens, R. C. Structure-guided inhibitor design for human FAAH by interspecies active site conversion Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 12820-12824
21. Mileni, M.; Garfunkle, J.; DeMartino, J. K.; Cravatt, B. F.; Boger, D. L.; Stevens, R. C. Binding and Inactivation Mechanism of a Humanized Fatty Acid Amide Hydrolase by alpha-Ketoheterocycle Inhibitors Revealed from Cocrystal Structures J. Am. Chem. Soc. 2009, 131, 10497-10506
22. Mileni, M.; Garfunkle, J.; Ezzili, C.; Kimball, F. S.; Cravatt, B. F.; Stevens, R. C.; Boger, D. L. X-ray Crystallographic Analysis of alpha-Ketoheterocycle Inhibitors Bound to a Humanized Variant of Fatty Acid Amide Hydrolase J. Med. Chem. 2010, 53, 230-240
23. Mileni, M.; Kamtekar, S.; Wood, D. C.; Benson, T. E.; Cravatt, B. F.; Stevens, R. C. Crystal Structure of Fatty Acid Amide Hydrolase Bound to the Carbamate Inhibitor URB597: Discovery of a Deacylating Water Molecule and Insight into Enzyme Inactivation J. Mol. Biol. 2010, 400, 743-754
24. Salam, N. K.; Nuti, R.; Sherman, W. Novel Method for Generating Structure-Based Pharmacophores Using Energetic Analysis J. Chem. Inf. Model. 2009, 49, 2356-2368
25. Loving, K.; Salam, N. K.; Sherman, W. Energetic analysis of fragment docking and application to structure-based pharmacophore hypothesis generation J. Comput. Aided Mol. Des. 2009, 23, 541-554
26. Barillari, C.; Marcou, G.; Rognan, D. Hot-spots-guided receptor-based pharmacophores (HS-Pharm): A knowledge-based approach to identify ligand-anchoring atoms in protein cavities and prioritize structure-based pharmacophores J. Chem. Inf. Model. 2008, 48, 1396-1410
27. Sun, H. M. Pharmacophore-based virtual screening Curr. Med. Chem. 2008, 15, 1018-1024
28. Carlson, H. A.; McCammon, J. A. Accommodating protein flexibility in computational drug design Mol. Pharmacol. 2000, 57, 213-218
29. Bowman, A. L.; Lerner, M. G.; Carlson, H. A. Protein flexibility and species specificity in structure-based drug discovery: Dihydrofolate reductase as a test system J. Am. Chem. Soc. 2007, 129, 3634-3640
30. Damm, K. L.; Carlson, H. A. Exploring experimental sources of multiple protein conformations in structure-based drug design J. Am. Chem. Soc. 2007, 129, 8225-8235
31. Lerner, M. G.; Bowman, A. L.; Carlson, H. A. Incorporating dynamics in E. coli dihydrofolate reductase enhances structure-based drug discovery J. Chem. Inf. Model. 2007, 47, 2358-2365
32. 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 http://www.rcsb.org/pdb/
33. Prime, version 2.2; Schrödinger, LLC: New York, 2010.
34. Impact, version 5.6; Schrödinger, LLC: New York, 2005.
35. Darden, T.; York, D.; Pedersen, L. Particle mesh ewald-an N.Log(N) method for Ewald sums in large systems J. Chem. Phys. 1993, 98, 10089-10092
36. Essmann, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. A smooth particle mesh Ewald method J. Chem. Phys. 1995, 103, 8577-8593
37. Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.; Hermans, J. In Intermolecular Forces; Pullman, B., Ed.; Reidel: Dordrecht, 1981; pp 331-342.
38. Desmond Molecular Dynamics System, version 2.4; D. E. Shaw Research: New York, 2010.
39. Maestro-Desmond Interoperability Tools, version 2.4; Schrödinger: New York, 2010.
40. Glide, version 5.6; Schrödinger, LLC: New York, 2010.
41. LigPrep, version 2.2; Schrödinger, LLC: New York, 2005.
42. Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shelley, M.; Perry, J. K.; Shaw, D. E.; Francis, P.; Shenkin, P. S. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy J. Med. Chem. 2004, 47, 1739-1749
43. Halgren, T. A.; Murphy, R. B.; Friesner, R. A.; Beard, H. S.; Frye, L. L.; Pollard, W. T.; Banks, J. L. Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening J. Med. Chem. 2004, 47, 1750-1759
44. Molecular Operating Environment, version 2010.10; Chemical Computing Group Inc.: Montreal, Canada, 2010.
45. Vacondio, F.; Silva, C.; Lodola, A.; Fioni, A.; Rivara, S.; Duranti, A.; Tontini, A.; Sanchini, S.; Clapper, J. R.; Piomelli, D.; Mor, M.; Tarzia, G. Structure-Property Relationships of a Class of Carbamate-Based Fatty Acid Amide Hydrolase (FAAH) Inhibitors: Chemical and Biological Stability ChemMedChem 2009, 4, 1495-1504
46. Davis, A. M.; St-Gallay, S. A.; Kleywegt, G. J. Limitations and lessons in the use of X-ray structural information in drug design Drug Discovery Today 2008, 13, 831-841
47. Minkkila, A.; Savinainen, J. R.; Kasnanen, H.; Xhaard, H.; Nevalainen, T.; Laitinen, J. T.; Poso, A.; Leppanen, J.; Saario, S. M. Screening of Various Hormone-Sensitive Lipase Inhibitors as Endocannabinoid-Hydrolyzing Enzyme Inhibitors ChemMedChem 2009, 4, 1253-1259
48. Mor, M.; Lodola, A.; Rivara, S.; Vacondio, F.; Duranti, A.; Tontini, A.; Sanchini, S.; Piersanti, G.; Clapper, J. R.; King, A. R.; Tarzia, G.; Piomelli, D. Synthesis and quantitative structure-activity relationship of fatty acid amide hydrolase inhibitors: Modulation at the N-portion of biphenyl-3-yl alkylcarbamates J. Med. Chem. 2008, 51, 3487-3498
49. Roughley, S.; Walls, S.; Hart, T.; Parsons, R.; Brough, P.; Graham, C.; Macias, A. Azetidine derivatives as inhibitors of fatty acid amide hydrolase useful in the treatment of diseases and preparation and pharmaceutical compositions thereof. WO2009109743, 2009.
50. Mor, M.; Rivara, S.; Lodola, A.; Plazzi, P. V.; Tarzia, G.; Duranti, A.; Tontini, A.; Piersanti, G.; Kathuria, S.; Piomelli, D. Cyclohexylcarbamic acid 3′- or 4′-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: Synthesis, quantitative structure-activity relationships, and molecular modeling studies J. Med. Chem. 2004, 47, 4998-5008
51. Min, X. S.; Thibault, S. T.; Porter, A. C.; Gustin, D. J.; Carlson, T. J.; Xu, H. D.; Lindstrom, M.; Xu, G. F.; Uyeda, C.; Ma, Z. H.; Li, Y. H.; Kayser, F.; Walker, N. P. C; Wang, Z. L. Discovery and molecular basis of potent noncovalent inhibitors of fatty acid amide hydrolase (FAAH) Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 7379-7384
52. Kimball, F. S.; Romero, F. A.; Ezzili, C.; Garfunkle, J.; Rayl, T. J.; Hochstatter, D. G.; Hwang, I.; Boger, D. L. Optimization of alpha-ketooxazole inhibitors of fatty acid amide hydrolase J. Med. Chem. 2008, 51, 937-947
53. Lexa, K. W.; Carlson, H. A. Full protein flexibility is essential for proper hot-spot mapping J. Am. Chem. Soc. 2011, 133, 200-202
54. Carlson, H. A. Protein flexibility is an important component of structure-based drug discovery Curr. Pharm. Design 2002, 8, 1571-1578