Cyclophilin a inhibition: Targeting transition-state-bound enzyme conformations for structure-based drug design

Journal of Chemical Information and Modeling

Volumn 53, Issue 2, 2013, Pages 403-410

  Nagaraju, Mulpuri ^a   McGowan, Lauren C ^a   Hamelberg, Donald ^a  

^a GEORGIA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CATALYSIS; ENZYME ACTIVITY; ISOMERIZATION; LEAD COMPOUNDS; MOLECULAR DYNAMICS; PEPTIDES;

CIS-TRANS ISOMERIZATION; COMPUTER AIDED DRUG DESIGN; CONFORMATIONAL ENSEMBLE; ENZYME-SUBSTRATE COMPLEXES; MOLECULAR DYNAMICS SIMULATIONS; POTENTIAL DRUG TARGETS; STRUCTURE BASED DRUG DESIGNS; X RAY CRYSTAL STRUCTURES;

ENZYME INHIBITION;

CYCLOPHILIN A; ENZYME INHIBITOR;

ARTICLE; CHEMISTRY; DRUG ANTAGONISM; DRUG DESIGN; ENZYME ACTIVE SITE; HUMAN; METABOLISM; MOLECULAR DYNAMICS; PROTEIN BINDING; PROTEIN CONFORMATION;

CATALYTIC DOMAIN; CYCLOPHILIN A; DRUG DESIGN; ENZYME INHIBITORS; HUMANS; MOLECULAR DYNAMICS SIMULATION; PROTEIN BINDING; PROTEIN CONFORMATION;

EID: 84874431865     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci300432w     Document Type: Article

References (65)

1. Handschumacher, R. E.; Harding, M. W.; Rice, J.; Drugge, R. J.; Speicher, D. W. Cyclophilin: a specific cytosolic binding protein for cyclosporin A Science 1984, 226, 544-547
2. Dornan, J.; Taylor, P.; Walkinshaw, M. D. Structures of immunophilins and their ligand complexes Curr. Top. Med. Chem. 2003, 3, 1392-1409
3. Galat, A. Peptidylprolyl cis/trans isomerases (immunophilins): biological diversity - targets - functions Curr. Top. Med. Chem. 2003, 3, 1315-1347
4. Fischer, G.; Wittmann-Liebold, B.; Lang, K.; Kiefhaber, T.; Schmid, F. X. Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins Nature 1989, 337, 476-478
5. Luban, J.; Bossolt, K. L.; Franke, E. K.; Kalpana, G. V.; Goff, S. P. Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B Cell 1993, 73, 1067-1078
6. Gamble, T. R.; Vajdos, F. F.; Yoo, S.; Worthylake, D. K.; Houseweart, M.; Sundquist, W. I.; Hill, C. P. Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid Cell 1996, 87, 1285-1294
7. Shen, J.; Person, M. D.; Zhu, J.; Abbruzzese, J. L.; Li, D. Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry Cancer Res. 2004, 64, 9018-9026
8. Howard, B. A.; Zheng, Z.; Campa, M. J.; Wang, M. Z.; Sharma, A.; Haura, E.; Herndon, J. E., 2nd; Fitzgerald, M. C.; Bepler, G.; Patz, E. F., Jr. Translating biomarkers into clinical practice: prognostic implications of cyclophilin A and macrophage migratory inhibitory factor identified from protein expression profiles in non-small cell lung cancer Lung Cancer 2004, 46, 313-323
9. Li, Z.; Zhao, X.; Bai, S.; Wang, Z.; Chen, L.; Wei, Y.; Huang, C. Proteomics identification of cyclophilin a as a potential prognostic factor and therapeutic target in endometrial carcinoma Mol. Cell Proteomics 2008, 7, 1810-1823
10. Theuerkorn, M.; Fischer, G.; Schiene-Fischer, C. Prolyl cis/trans isomerase signalling pathways in cancer Curr. Opin. Pharmacol. 2011, 11, 281-287
11. Luo, C.; Luo, H.; Zheng, S.; Gui, C.; Yue, L.; Yu, C.; Sun, T.; He, P.; Chen, J.; Shen, J.; Luo, X.; Li, Y.; Liu, H.; Bai, D.; Yang, Y.; Li, F.; Zuo, J.; Hilgenfeld, R.; Pei, G.; Chen, K.; Shen, X.; Jiang, H. Nucleocapsid protein of SARS coronavirus tightly binds to human cyclophilin A Biochem. Biophys. Res. Commun. 2004, 321, 557-565
12. Capano, M.; Virji, S.; Crompton, M. Cyclophilin-A is involved in excitotoxin-induced caspase activation in rat neuronal B50 cells Biochem. J. 2002, 363, 29-36
13. Dawson, T. M.; Steiner, J. P.; Lyons, W. E.; Fotuhi, M.; Blue, M.; Snyder, S. H. The immunophilins, FK506 binding protein and cyclophilin, are discretely localized in the brain: relationship to calcineurin Neuroscience 1994, 62, 569-580
14. Daum, S.; Schumann, M.; Mathea, S.; Aumuller, T.; Balsley, M. A.; Constant, S. L.; de Lacroix, B. F.; Kruska, F.; Braun, M.; Schiene-Fischer, C. Isoform-specific inhibition of cyclophilins Biochemistry 2009, 48, 6268-6277
15. Sambasivarao, S. V.; Acevedo, O. Computational Insight into Small Molecule Inhibition of Cyclophilins J. Chem. Inf. Model. 2011, 51, 475-482
16. Acevedo, O.; Ambrose, Z.; Flaherty, P. T.; Aamer, H.; Jain, P.; Sambasivarao, S. V. Identification of HIV inhibitors guided by free energy perturbation calculations Curr. Pharm. Des. 2012, 18, 1199-1216
17. Siekierka, J. J.; Hung, S. H.; Poe, M.; Lin, C. S.; Sigal, N. H. A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin Nature 1989, 341, 755-757
18. Sedrani, R.; Kallen, J.; Martin Cabrejas, L. M.; Papageorgiou, C. D.; Senia, F.; Rohrbach, S.; Wagner, D.; Thai, B.; Jutzi Eme, A. M.; France, J.; Oberer, L.; Rihs, G.; Zenke, G.; Wagner, J. Sanglifehrin-cyclophilin interaction: degradation work, synthetic macrocyclic analogues, X-ray crystal structure, and binding data J. Am. Chem. Soc. 2003, 125, 3849-3859
19. Calne, R. Y.; Collier, D. S.; Lim, S.; Pollard, S. G.; Samaan, A.; White, D. J.; Thiru, S. Rapamycin for immunosuppression in organ allografting Lancet 1989, 334 (8656) 227-227
20. Hojo, M.; Morimoto, T.; Maluccio, M.; Asano, T.; Morimoto, K.; Lagman, M.; Shimbo, T.; Suthanthiran, M. Cyclosporine induces cancer progression by a cell-autonomous mechanism Nature 1999, 397, 530-534
21. Jorgensen, W. L. The many roles of computation in drug discovery Science 2004, 303, 1813-1818
22. Leach, A. R.; Shoichet, B. K.; Peishoff, C. E. Prediction of protein-ligand interactions. Docking and scoring: successes and gaps J. Med. Chem. 2006, 49, 5851-5855
23. Perola, E.; Walters, W. P.; Charifson, P. S. A detailed comparison of current docking and scoring methods on systems of pharmaceutical relevance Proteins 2004, 56, 235-249
24. 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
25. Zhou, Z.; Felts, A. K.; Friesner, R. A.; Levy, R. M. Comparative performance of several flexible docking programs and scoring functions: enrichment studies for a diverse set of pharmaceutically relevant targets J. Chem. Inf. Model. 2007, 47, 1599-1608
26. Cavasotto, C. N.; Kovacs, J. A.; Abagyan, R. A. Representing receptor flexibility in ligand docking through relevant normal modes J. Am. Chem. Soc. 2005, 127, 9632-9640
27. Zavodszky, M. I.; Lei, M.; Thorpe, M. F.; Day, A. R.; Kuhn, L. A. Modeling correlated main-chain motions in proteins for flexible molecular recognition Proteins 2004, 57, 243-261
28. Schnecke, V.; Swanson, C. A.; Getzoff, E. D.; Tainer, J. A.; Kuhn, L. A. Screening a peptidyl database for potential ligands to proteins with side-chain flexibility Proteins 1998, 33, 74-87
29. Alberts, I. L.; Todorov, N. P.; Dean, P. M. Receptor flexibility in de novo ligand design and docking J. Med. Chem. 2005, 48, 6585-6596
30. Adcock, S. A.; McCammon, J. A. Molecular dynamics: survey of methods for simulating the activity of proteins Chem. Rev. 2006, 106, 1589-1615
31. Lin, J. H.; Perryman, A. L.; Schames, J. R.; McCammon, J. A. Computational drug design accommodating receptor flexibility: the relaxed complex scheme J. Am. Chem. Soc. 2002, 124, 5632-5633
32. Perryman, A. L.; Lin, J. H.; Andrew McCammon, J. Optimization and computational evaluation of a series of potential active site inhibitors of the V82F/I84V drug-resistant mutant of HIV-1 protease: an application of the relaxed complex method of structure-based drug design Chem. Biol. Drug. Des. 2006, 67, 336-345
33. Lin, J. H.; Perryman, A. L.; Schames, J. R.; McCammon, J. A. The relaxed complex method: Accommodating receptor flexibility for drug design with an improved scoring scheme Biopolymers 2003, 68, 47-62
34. Craig, I. R.; Essex, J. W.; Spiegel, K. Ensemble docking into multiple crystallographically derived protein structures: an evaluation based on the statistical analysis of enrichments J. Chem. Inf. Model. 2010, 50, 511-524
35. Rao, S.; Sanschagrin, P. C.; Greenwood, J. R.; Repasky, M. P.; Sherman, W.; Farid, R. Improving database enrichment through ensemble docking J. Comput. Aided. Mol. Des. 2008, 22, 621-627
36. Limongelli, V.; Marinelli, L.; Cosconati, S.; Braun, H. A.; Schmidt, B.; Novellino, E. Ensemble-docking approach on BACE-1: pharmacophore perception and guidelines for drug design Chem. Med. Chem. 2007, 2, 667-678
37. Huang, S. Y.; Zou, X. Ensemble docking of multiple protein structures: considering protein structural variations in molecular docking Proteins 2007, 66, 399-421
38. Nichols, S. E.; Baron, R.; Ivetac, A.; McCammon, J. A. Predictive power of molecular dynamics receptor structures in virtual screening J. Chem. Inf. Model. 2011, 51, 1439-1446
39. McGovern, S. L.; Shoichet, B. K. Information decay in molecular docking screens against holo, apo, and modeled conformations of enzymes J. Med. Chem. 2003, 46, 2895-2907
40. Wolfenden, R. Transition State Analog Inhibitors and Enzyme Catalysis Annu. Rev. Biophys. Bioeng. 1976, 5, 271-306
41. Mikol, V.; Papageorgiou, C.; Borer, X. The role of water molecules in the structure-based design of (5-hydroxynorvaline)-2-cyclosporin: synthesis, biological activity, and crystallographic analysis with cyclophilin A J. Med. Chem. 1995, 38, 3361-3367
42. Ni, S.; Yuan, Y.; Huang, J.; Mao, X.; Lv, M.; Zhu, J.; Shen, X.; Pei, J.; Lai, L.; Jiang, H.; Li, J. Discovering potent small molecule inhibitors of cyclophilin A using de novo drug design approach J. Med. Chem. 2009, 52, 5295-5298
43. Wu, Y. Q.; Belyakov, S.; Choi, C.; Limburg, D.; Thomas, I. B.; Vaal, M.; Wei, L.; Wilkinson, D. E.; Holmes, A.; Fuller, M.; McCormick, J.; Connolly, M.; Moeller, T.; Steiner, J.; Hamilton, G. S. Synthesis and biological evaluation of non-peptidic cyclophilin ligands J. Med. Chem. 2003, 46, 1112-1115
44. Guichou, J.-F.; Colliandre, L.; Ahmed-Belkacem, H.; Pawlotsky, J.-M. New inhibitors of cyclophilins and uses thereof. Patent WO2011076784, 2011.
45. Ma, B.; Nussinov, R. Enzyme dynamics point to stepwise conformational selection in catalysis Curr. Opin. Chem. Biol. 2010, 14, 652-659
46. Kollman, P. A.; Massova, I.; Reyes, C.; Kuhn, B.; Huo, S.; Chong, L.; Lee, M.; Lee, T.; Duan, Y.; Wang, W.; Donini, O.; Cieplak, P.; Srinivasan, J.; Case, D. A.; Cheatham, T. E., 3rd Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models Acc. Chem. Res. 2000, 33, 889-897
47. Doshi, U.; McGowan, L. C.; Ladani, S. T.; Hamelberg, D. Resolving the complex role of enzyme conformational dynamics in catalytic function Proc. Natl. Acad. Sci. U S A 2012, 109, 5699-5704
48. Hamelberg, D.; McCammon, J. A. Mechanistic insight into the role of transition-state stabilization in cyclophilin A J. Am. Chem. Soc. 2009, 131, 147-152
49. Trott, O.; Olson, A. J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading J. Comput. Chem. 2010, 30, 455-461
50. Lu, Y.; Yang, C. Y.; Wang, S. Binding free energy contributions of interfacial waters in HIV-1 protease/inhibitor complexes J. Am. Chem. Soc. 2006, 128, 11830-11839
51. Garcia-Sosa, A. T.; Mancera, R. L. Free Energy Calculations of Mutations Involving a Tightly Bound Water Molecule and Ligand Substitutions in a Ligand-Protein Complex Mol. Inf. 2010, 29, 589-600
52. de Beer, S. B.; Vermeulen, N. P.; Oostenbrink, C. The role of water molecules in computational drug design Curr. Top. Med. Chem. 2010, 10, 55-66
53. Hamelberg, D.; McCammon, J. A. Standard free energy of releasing a localized water molecule from the binding pockets of proteins: double-decoupling method J. Am. Chem. Soc. 2004, 126, 7683-7689
54. Lam, P. Y.; Jadhav, P. K.; Eyermann, C. J.; Hodge, C. N.; Ru, Y.; Bacheler, L. T.; Meek, J. L.; Otto, M. J.; Rayner, M. M.; Wong, Y. N. Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors Science 1994, 263, 380-384
55. Chen, J. M.; Xu, S. L.; Wawrzak, Z.; Basarab, G. S.; Jordan, D. B. Structure-based design of potent inhibitors of scytalone dehydratase: displacement of a water molecule from the active site Biochemistry 1998, 37, 17735-17744
56. Li, Z.; Lazaridis, T. Water at biomolecular binding interfaces Phys. Chem. Chem. Phys. 2007, 9, 573-581
57. Connelly, P. R.; Aldape, R. A.; Bruzzese, F. J.; Chambers, S. P.; Fitzgibbon, M. J.; Fleming, M. A.; Itoh, S.; Livingston, D. J.; Navia, M. A.; Thomson, J. A. Enthalpy of hydrogen bond formation in a protein-ligand binding reaction Proc. Natl. Acad. Sci. USA 1994, 91, 1964-1968
58. Vajdos, F. F.; Yoo, S.; Houseweart, M.; Sundquist, W. I.; Hill, C. P. Crystal structure of cyclophilin A complexed with a binding site peptide from the HIV-1 capsid protein Protein Sci. 1997, 6, 2297-2307
59. Case, D. A.; Darden, T. A.; Cheatham, I., T. E.; Simmerling, C. L.; Wang, J.; Duke, R. E.; Luo, R.; Crowley, M.; Walker, R. C.; Zhang, W.; Merz, K. M.; Wang, B.; Hayik, S.; Roitberg, A.; Seabra, G.; Kolossváry, I.; Wong, K. F.; Paesani, F.; Vanicek, J.; Wu, X.; Brozell, S. R.; Steinbrecher, T.; Gohlke, H.; Yang, L.; Tan, C.; Mongan, J.; Hornak, V.; Cui, G.; Mathews, D. H.; Seetin, M.G.;; Sagui, C.; Babin, V.; Kollman, P. A. AMBER 10; University of California, San Francisco; 2008.
60. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of simple potential functions for simulating liquid water J. Chem. Phys. 1983, 79, 926-935
61. Cornell, W. D.; Cieplak, P.; Christopher, I. B.; Gould, I. R.; Merz, J. K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules J. Am. Chem. Soc. 1995, 117, 5179-5197
62. Urmi, D.; Hamelberg, D. Reoptimization of the AMBER Force Field Parameters for Peptide Bond (Omega) Torsions Using Accelerated Molecular Dynamics J. Phys. Chem. B 2009, 113, 16590-16595
63. 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
64. Ryckaert, J. P.; Ciccotti, G.; Berendsen, H. J. C. Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes J. Comput. Phys. 1977, 23, 327-341
65. Dennington, R., II; Keith, T.; Millam, J. Gaussview, version 3.09; Semichem, Inc., Shawnee Mission, KS, 2003.