Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors: Prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculations

Journal of Chemical Information and Modeling

Volumn 49, Issue 4, 2009, Pages 886-899

  Alzate Morales, Jans H ^a   Caballero, Julio ^a   Jague, Ariela Vergara ^a   Nilo, Fernando D González ^a  

^a UNIVERSIDAD DE TALCA   (Chile)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING SITES; BIOACTIVITY; LIGANDS; POSITIVE IONS; PROTEINS; QUANTUM CHEMISTRY;

CORRELATION COEFFICIENT; CORRELATION MODELING; CYCLIN-DEPENDENT KINASE; PROTEIN-LIGAND INTERACTIONS; PROTEIN-LIGAND STRUCTURES; QUANTUM CHEMICAL DESCRIPTOR; QUANTUM CHEMICAL DESCRIPTORS; SINGLE-POINT ENERGY;

BINDING ENERGY;

CYCLIN DEPENDENT KINASE 2; DRUG DERIVATIVE; ENZYME INHIBITOR; GUANINE;

ALGORITHM; ARTICLE; CHEMICAL STRUCTURE; CRYSTALLIZATION; DRUG ANTAGONISM; ENERGY TRANSFER; FACTUAL DATABASE; FORECASTING; HYDROGEN BOND; PROTEIN BINDING; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ALGORITHMS; CRYSTALLIZATION; CYCLIN-DEPENDENT KINASE 2; DATABASES, FACTUAL; ENERGY TRANSFER; ENZYME INHIBITORS; FORECASTING; GUANINE; HYDROGEN BONDING; MODELS, MOLECULAR; PROTEIN BINDING; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 66149138737     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci8004034     Document Type: Article

References (53)

1. Norbury, C.; Nurse, P. Animal-Cell Cycles and Their Control. Annu. Rev. Biochem. 1992, 61, 441-4170.
2. Morgan, D. O. Principles of CDK Regulation. Nature (London) 1995, 374 (6518), 131-134.
3. Hall, M.; Peters, G. Genetic alterations of cyclins, cyclin-dependent kinases and Cdk inhibitors in human cancer. Adv. Cancer Res. 1996, 68, 67-108.
4. Sielecki, T. M.; Boylan, J. F.; Benfield, P. A.; Trainor, G. L. Cyclin-dependent kinase inhibitors: Useful targets in cell cycle regulation. J. Med. Chem. 2000, 43 (1), 1-18.
5. Watanabe, N.; Broome, M.; Hunter, T. Regulation of the Human WEE1HU CDK Tyrosine 15-Kinase during the Cell-Cycle. EMBO J. 1995, 14 (9), 1878-1891.
6. Coulonval, K.; Bockstaele, L.; Paternot, S.; Roger, P. P. Phosphory-lations of cyclin-dependent kinase 2 revisited using two-dimensional gel electrophoresis. J. Biol Chem. 2003, 278 (52), 52052-52060.
7. Pavletich, N. P. Mechanisms of cyclin-dependent kinase regulation: Structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J. Mol. Biol. 1999, 287 (5), 821-828.
8. Losiewicz, M. D.; Carlson, B. A.; Kaur, G.; Sausville, E. A.; Worland, P. J. Potent Inhibition of CDC2 Kinase-Activity by the Flavonoid L86-8275. Biochem. Biophys. Res. Commun. 1994, 201 (2), 589-595.
9. Senderowicz, A. M.; Sausville, E. A. Preclinical and clinical development of cyclin-dependent kinase modulators. J. Natl. Cancer Inst. 2000, 92 (5), 376-387.
10. Hardcastle, I. R.; Golding, B. T.; Griffin, R. J. Designing inhibitors of cyclin-dependent kinases. Annu. Rev. Pharmacol. Toxicol. 2002, 42, 325-348.
11. Knockaert, M.; Greengard, P.; Meijer, L. Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol. Sci. 2002, 23 (9), 417-425.
12. Toogood, P. L. Progress toward the development of agents to modulate the cell cycle. Curr. Opin. Chem. Biol. 2002, 6 (4), 472-478.
13. Shapiro, G. I. Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol. Clin. Cancer Res. 2004, 10, 4270S-4275S.
14. Vieth, M.; Higgs, R.; Robertson, D.; Shapiro, M.; Gragg, E.; Hemmerle, H. Kinomics-structural biology and chemogenomics of kinase inhibitors and targets. Biochim. Biophys. Acta 2004, 1697 (1-2), 243-57.
15. Fernandez, M.; Tudidor-Camba, A.; Caballero, J. Modeling of cyclin-dependent kinase inhibition by lH-pyrazolo[3,4-d]pyrimidine derivatives using artificial neural network ensembles. J. Chem. Inf. Model. 2005, 45 (6), 1884-1895.
16. Gonzalez, M. P.; Caballero, J.; Morales Helguera, A.; Garriga, M.; Gonzalez, G.; Fernandez, M. 2D autocorrelation modelling of the inhibitory activity of cytokinin-derived cyclin-dependent kinase inhibitors. Bull. Math. Biol. 2006, 68 (4), 735-751.
17. Dureja, H.; Madan, A. K. Topochemical models for prediction of cyclin-dependent kinase 2 inhibitory activity of indole-2-ones. J. Mol. Model. 2005, 11 (6), 525-531.
18. Li, J. Z.; Liu, H. X.; Yao, X. J.; Liu, M. C.; Hu, Z. D.; Fan, B. T. Structure-activity relationship study of oxindole-based inhibitors of cyclin-dependent kinases based on least-squares support vector machines. Anal. Chim. Acta 2007, 581 (2), 333-342.
19. Samanta, S.; Debnath, B.; Basu, A.; Gayen, S.; Srikanth, K.; Jha, T. Exploring QSAR on 3-aminopyrazoles as antitumor agents for their inhibitory activity of CDK2/cyclin A. Eur. J. Med. Chem. 2006, 41 (10), 1190-1195.
20. Alzate-Morales, J. H.; Contreras, R.; Soriano, A.; Tunon, I.; Silla, E. A computational study of the protein-ligand interactions in CDK2 inhibitors: Using quantum mechanics/molecular mechanics interaction energy as a predictor of the biological activity. Biophys. J. 2007, 92 (2), 430-439.
21. Alzate-Morales, J. H.; Tiznado, W.; Santos, J. C.; Cardenas, C.; Contreras, R. Theoretical study on CDK2 inhibitors using a global softness obtained from the density of states. J. Phys. Chem. B 2007, 111 (12), 3293-3297.
22. Hardcastle, I.; Arris, C.; Bentley, J.; Boyle, F.; Chen, Y.; Curtin, N.; Endicott, J.; Gibson, A.; Golding, B.; Griffin, R.; Jewsbury, P.; Menyerol, J.; Mesguiche, V.; Newell, D.; Noble, M.; Pratt, D.; Wang, L.; Whitfield, H. N2-substituted 06-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2. J. Med. Chem. 2004, 47 (15), 3710-3722.
23. Gibson, A.; Arris, C.; Bentley, J.; Boyle, F.; Curtin, N.; Davies, T.; Endicott, J.; Golding, B.; Grant, S.; Griffin, R.; Jewsbury, P.; Johnson, L.; Mesguiche, V.; Newell, D.; Noble, M.; Tucker, J.; Whitfield, H. Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives. J. Med. Chem. 2002, 45 (16), 3381-3393.
24. Griffin, R.; Henderson, A.; Curtin, N.; Echalier, A.; Endicott, J.; Hardcastle, I.; Newell, D.; Noble, M.; Wang, L.; Golding, B. Searching for cyclin-dependent kinase inhibitors using a new variant of the cope elimination. J. Am. Chem. Soc. 2006, 128 (18), 6012-6013.
25. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 1998, 19 (14), 1639-1662.
26. Meng, E. C.; Gschwend, D. A.; Blaney, J. M.; Kuntz, I. D. Orientational Sampling and Rigid-Body Minimization in Molecular Docking. Proteins 1993, 17 (3), 266-278.
27. Blaney, J.; Dixon, J. A good ligand is hard to find: Automated docking methods. Perspect. Drug Discovery Des. 1993, 1, 301-319.
28. Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. Development and use of quantum mechanical molecular models. 76. AM1: a new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 1985, 107, 3902-3909.
29. Stewart, J. J. P. MOPAC, version 6; Fujitsu Limited: Tokyo, Japan, 2006.
30. Insight II, version 2005; Accelrys Inc.: San Diego, CA, 2005.
31. Dauberosguthorpe, P.; Roberts, V. A.; Osguthorpe, D. J.; Wolff, J.; Genest, M.; Hagler, A. T. Structure and energetics of ligand-binding to proteins - Escherichia-coli dihydrofolate reductase trimethoprim, a drug-receptor system. Proteins 1988, 4 (1), 31-47.
32. Sanner, M. F. Python: A programming language for software integration and development. J. Mol. Graphics Modell. 1999, 17(1), 57-61.
33. Berman, H.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.; Weissig, H.; Shindyalov, I.; Bourne, P. The Protein Data Bank. Nucleic Acids Res. 2000, 28 (1), 235-242.
34. Bartova, I.; Koca, J.; Otyepka, M. Functional flexibility of human cyclin-dependent kinase-2 and its evolutionary conservation. Protein Sci. 2008, 17 (1), 22-33.
35. Duca, J. S.; Madison, V. S.; Voigt, J. H. Cross-docking of inhibitors into CDK2 structures. 1. J. Chem. Inf. Model. 2008, 48 (3), 659-668.
36. May, A.; Zacharias, M. Protein-ligand docking accounting for receptor side chain and global flexibility in normal modes: Evaluation on kinase inhibitor cross docking. J. Med. Chem. 2008, 51 (12), 3499-3506.
37. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.: Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, L.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision A.1; Gaussian, Inc.: Pittsburgh, PA, 2003.
38. Svensson, M.; Humbel, S.; Froese, R. D.J.; Matsubara, T.; Sieber, S.; Morokuma, K. ONIOM: A multilayered integrated MO+MM method for geometry optimizations and single point energy predictions. A test for Diels-Alder reactions and Pt(P(t-Bu)(3))(2)+H-2 oxidative addition. J. Phys. Chem. 1996, 100 (50), 19357-19363.
39. Dapprich, S.; Komaromi, I.; Byun, K. S.; Morokuma, K.; Frisch, M. J. A new ONIOM implementation in Gaussian98 Part I. The calculation of energies, gradients, vibrational frequencies and electric field derivatives. J. Mol. Struct.: Theochem 1999, 462, 1-21.
40. Froese, R. D. J.; Morokuma, K. Hybrid methods. In Encyclopedia of Computational Chemistry; Schleyer, P.v. R., Ed.; John Wiley and Sons: Chichester, Sussex, 1998; Vol. 2, pp 1244-1257.
41. Zhou, T.; Huang, D.; Caflisch, A. Is quantum mechanics necessary for predicting binding free energy. J. Med. Chem. 2008, 51 (14), 4280-4288.
42. Namasivayam, V.; Günther, R. PSO@AUTODOCK: A fast flexible molecular docking program based on swarm intelligence. Chem. Biol. Drug Des. 2007, 70 (6), 475-484.
43. Kellenberger, E.; Rodrigo, J.; Muller, P.; Rognan, D. Comparative evaluation of eight docking tools for docking and virtual screening accuracy. Proteins: Struct., Funct. Bioinf. 2004, 57 (2), 225-242.
44. Warren, G. L.; Andrews, C. W.; Capelli, A. M.; Clarke, B.; LaLonde, J.; Lambert, M. H.; Lindvall, M.; Nevins, N.; Semus, S. F.; Senger, S.; Tedesco, G.; Wall, I. D.; Woolven, J. M.; Peishoff, C. E.; Head, M. S. A critical assessment of docking programs and scoring functions. J. Med. Chem. 2006, 49 (20), 5912-5931.
45. Arris, C. E.; Boyle, F. T.; Calvert, A. H.; Curtin, N. J.; Endicott, J. A.; Garman, E. F.; Gibson, A. E.; Golding, B. T.; Grant, S.; Griffin, R. J.; Jewsbury, P.; Johnson, L. N.; Lawrie, A. M.; Newell, D. R.; Noble, M. E. M.; Sausville, E. A.; Schultz, R.; Yu, W. Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. J. Med. Chem. 2000, 43 (15), 2797-2804.
46. Davies, T. G.; Bentley, J.; Arris, C. E.; Boyle, F. T.; Curtin, N. J.; Endicott, J. A.; Gibson, A. E.; Golding, B. T.; Griffin, R. J.; Hardcastle, I. R.; Jewsbury, P.; Johnson, L. N.; Mesguiche, V.; Newell, D. R.; Noble, M. E. M.; Tucker, J. A.; Wang, L.; Whitfield, H. J. Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor. Nat. Struct. Biol. 2002, 9 (10), 745-749.
47. Davies, T. G.; Pratt, D. J.; Endicott, J. A.; Johnson, L. N.; Noble, M. E. Structure-based design of cyclin-dependent kinase inhibitors. Pharmacol. Ther. 2002, 93, 125-133.
48. Aixiao, L.; Florent, B.; Francois, M.; Michel, D.; Baoshan, W. Interaction mode and selectivity of the 2PU inhibitor with the CDK4 and CDK2 cyclin-dependant kinases: A molecular dynamics study. J. Mol. Struct.: Theochem 2008, 849 (1-3), 62-75.
49. Sun, M.; Li, Z. S.; Zhang, Y.; Zheng, Q. C.; Sun, C. C. Homology modeling and docking study of cyclin-dependent kinase (CDK) 10. Bioorg. Med. Chem. Lett. 2005, 15 (11), 2851-2856.
50. Jiang, Y. J.; Zou, J. W.; Gui, C. S. Study of a ligand complexed with Cdk2/Cdk4 by computer simulation. J. Mol. Model. 2005, 11 (6), 509-515.
51. Lyne, P. D.; Lamb, M. L.; Saeh, J. C. Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. J. Med. Chem. 2006, 49 (16), 4805-4808.
52. 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 (7), 1739-1749.
53. Huang, N.; Kalyanaraman, C.; Irwin, J. J.; Jacobson, M. P. Physics-based scoring of protein-ligand complexes: Enrichment of known inhibitors in large-scale virtual screening. J. Chem. Inf. Model. 2006, 46, 243-253.